The link between pesticides and cancer has long been a concern. While agriculture has traditionally been tied to pesticide-related illnesses, 19 of 30 commonly used lawn pesticides and 28 of 40 commonly used school pesticides are linked to cancer. Even with the growing body of evidence linking environmental exposures to cancer in recent years, a report released May 6, 2010 by the President’s Cancer Panel finds that the true burden of environmentally-induced cancer is greatly underestimated. The Panel’s report, Reducing Environmental Cancer Risk: What We Can Do Now, concludes that while environmental exposure is not a new front on the war on cancer, the grievous harm from carcinogenic chemical use has not been addressed adequately by the nation’s cancer program.

Occupational exposure to pesticides and bladder cancer risk.Study used data from the Agricultural Health Study, a prospective cohort study which includes 57 310 pesticide applicators with detailed information on pesticide use, to evaluate the association between pesticides and bladder cancer. Results found associations with bladder cancer risk for two imidazolinone herbicides, imazethapyr and imazaquin, which are aromatic amines. Ever use of imazaquin was associated with increased risk whereas the excess risk among users of imazethapyr was evident among never smokers. Study also observed increased risks overall and among never smokers for use of several chlorinated pesticides including chlorophenoxy herbicides and organochlorine insecticides. Several associations between specific pesticides and bladder cancer risk were observed, many of which were stronger among never smokers, suggesting that possible risk factors for bladder cancer may be more readily detectable in those unexposed to potent risk factors like tobacco smoke.[Koutros S, Silverman DT, Alavanja MC, Andreotti G, et al. 2015. Int J Epidemiol. pii: dyv195.]

Diuron-induced rat urinary bladder carcinogenesis: mode of action and human relevance evaluations using the International Programme on Chemical Safety framework.Diuron, a high volume substituted urea herbicide, induced high incidences of urinary bladder carcinomas and low incidences of kidney pelvis papillomas and carcinomas in rats exposed to high doses (2500 ppm) in a 2-year bioassay. Diuron is registered for both occupational and residential uses and is used worldwide for more than 30 different crops. The proposed rat urothelial mode of action (MOA) for this herbicide consists of metabolic activation to metabolites that are excreted and concentrated in the urine, leading to cytotoxicity, urothelial cell necrosis and exfoliation, regenerative hyperplasia, and eventually tumors. Authors show evidence for this MOA for diuron using the International Programme on Chemical Safety (IPCS) conceptual framework for evaluating an MOA for chemical carcinogens, and the United States Environmental Protection Agency (USEPA) and IPCS framework for assessing human relevance.[Da Rocha MS, Arnold LL, De Oliveira ML, Catalano SM, et al. 2014. Crit Rev Toxicol. 44(5):393-406.]

Gene environment interaction in urinary bladder cancer with special reference to organochlorine pesticide: a case control study.Urinary bladder cancer (UBC) is a common disease worldwide with a higher incidence rate in developed countries. Organochlorine pesticides (OCPs), potent endocrine disrupters, are found to be associated with several cancers such as prostate, breast, bladder, etc. The present study was carried out in UBC subjects and healthy control subjects with an aim to determine the role of Glutathione S-transferase (GST) and GSTT1 polymorphism and its implication on the OCP detoxification or bioaccumulation which may increase the risk of UBC in humans. This study was also designed to identify the "gene-environment interaction" specifically between gene polymorphism in xenobiotic metabolizing genetic enzyme(s) and blood OCP levels. The results demonstrated a significant increase in frequency of GSTM1/GSTT1(null) genotype in UBC cases without interfering the distribution of other GSTT1/GSTM1 genotypes. Findings indicate that "gene-environment interaction" may play a key role in increasing the risk for UBC in individuals who are genetically more susceptible due to presence of GSTM1/GSTT1 null deletion during their routine encounter with or exposure to OCPs.[Sharma T, Jain S, Verma A et al. 2013. Cancer Biomark.13(4):243-51]

Bone Cancer

Risk of childhood cancers associated with residence in agriculturally intense areas in the United StatesAn ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with agricultural activity finds an elevated risk for malignant bone tumors (OR 2.3) and for subtype osteosarcoma (OR 2.7) at high agricultural activity (greater than 60% of county acreage devoted to farming). Also linked to Ewing’s sarcoma (OR 4.3) and HL (OR 2.1) at high agricultural activity (greater than 60% of county acreage devoted to farming), and for oat crop acreage and Ewing’s (OR 2.3).[Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]

Ewing’s bone sarcoma, paternal occupational exposure, and other factorsA study of Ewing’s bone sarcoma patients shows an elevated risk for children whose fathers are engaged in agricultural occupations during the period from six months prior to conception of the patient to the time of diagnosis (8.8 OR) and for children whose fathers had occupational exposure to herbicides, pesticides, or fertilizers (6.1 OR).[Holly, E.A., at al. 1992. Am J Epidemiol 135(2):122-129.]

Brain Cancer

Childhood Brain Cancer

Exposure to pyrethroid pesticides and the risk of childhood brain tumors in East ChinaPesticide exposure is hypothesized as one of the risk factors for the development of childhood brain tumors (CBT). This hospital-based case-control study evaluated the association of pyrethroid pesticide exposure with the risk for CBT in a children population in East China. In total, 161 CBT cases and 170 controls were recruited from 2 children's medical centers in Shanghai (Xinhua Hospital and Shanghai Children's Medical Center) between September 2012 and June 2015. The cases and controls were matched for age, sex, and province of residence. Pyrethroid pesticide exposure was evaluated by urinalysis of 3 nonspecific metabolites of pyrethroids (cis-DCCA, trans-DCCA, and 3-PBA) using gas chromatography-mass spectrometry (GC-MS) detection and by administering a questionnaire. Unconditional logistic regression showed that trans-DCCA, 3-PBA, and total metabolites (sum of the 3 metabolites) were positively associated with the increased risk of CBT. Children in the highest quartile had a nearly 3-fold increased risk of CBT compared with those in the lowest quartile after adjusting for confounding factors (trans-DCCA, odds ratio (OR) = 2.58, 95% confidence interval (CI), 1.38-4.80, p = 0.003; 3-PBA, OR = 3.26, 95% CI, 1.73-6.14, p < 0.0001; total metabolites, OR = 3.60, 95% CI, 1.87-6.93, p < 0.0001). We also found that exposure to both mosquitocide and cockroach killer was related to the increased risk of CBT (mosquitocide, OR = 1.68, 95% CI, 1.06-2.67, p = 0.027; cockroach killer, OR = 1.83, 95% CI, 1.13-2.95, p = 0.013). These findings indicate that exposure to pyrethroid pesticides might be associated with increased risk of CBT. Prospective cohort studies with larger sample sizes are required to confirm this conclusion[Chen S, Gu S, Wang Y, Yao Y, et al. 2016. Environ Pollut. 218:1128-1134.]

Increased risk of childhood brain tumors among children whose parents had farm-related pesticide exposures during pregnancy.Malignant brain tumors rank second in both incidence and mortality by cancer in children, and they are the leading cause of cancer death in children. While there are several studies which link pesticide exposure to increased risk of CBT, findings have been inconsistent. Authors performed a meta-analysis on 15 published epidemiological studies to test that in utero exposure to pesticides may be involved in the development of brain cancer in children. Findings of meta-analyses revealed a significantly increased risk of CBT among children whose mothers had farm-related exposures during pregnancy (RR=1.48, 95% CI=1.18-1.84). A dose response was recognized when this risk estimate was compared to those for risk of CBT from maternal exposure to non-agricultural pesticides (e.g., home extermination, pest strips) during pregnancy (RR=1.36, 1.10-1.68), and risk of CBT among children exposed to agricultural activities (RR=1.32, 1.04-1.67). Three studies combined for the paternal exposure to pesticides during preconception produced a calculated summary risk estimate of odds ratio (OR) = 2.29 (95% CI: 1.39-3.78). Meta-analysis of five studies of paternal exposure to pesticides during pregnancy produced a final calculated summary risk estimate of OR = 1.63 (95% CI: 1.16-2.31). The search of the CTD databases revealed association between herbicide and astrocytoma and more than 300 genes are altered by exposure to herbicide, fungicide, insecticide or pesticides. Based on the collective results of these meta-analyses, it appears that pesticide exposure may increase risk of CBT, with preconception and prenatal exposures being especially important factors in increasing risk of its development.[Kunkle B, Bae S, Singh KP, Roy D. 2014. JP J Biostat. 11(2):89-101]

Exposure to pesticides and the risk of childhood brain tumors.Previous research has suggested positive associations between parental or childhood exposure to pesticides and risk of childhood brain tumors (CBT). This Australian case-control study of CBT investigated whether exposures to pesticides before pregnancy, during pregnancy and during childhood, were associated with an increased risk.Cases were recruited from 10 pediatric oncology centers, and controls by random-digit dialing, frequency matched on age, sex, and State of residence. The odds ratios (ORs) for professional pest control treatments in the home in the year before the index pregnancy, during the pregnancy, and after the child's birth were 1.54 (95% confidence interval (CI): 1.07, 2.22), 1.52 (95% CI: 0.99, 2.34) and 1.04 (95% CI: 0.75, 1.43), respectively. ORs for treatments exclusively before pregnancy and during pregnancy were 1.90 (95% CI: 1.08, 3.36) and 1.02 (95% CI: 0.35, 3.00), respectively. The OR for the father being home during the treatment was 1.79 (95% CI: 0.85, 3.80). The OR for paternal occupational exposure in the year before the child's conception was 1.36 (95% CI: 0.66, 2.80). ORs for prenatal home pesticide exposure were elevated for low- and high-grade gliomas; effect estimates for other CBT subtypes varied and lacked precision.These results suggest that preconception pesticide exposure, and possibly exposure during pregnancy, is associated with an increased CBT risk. It may be advisable for both parents to avoid pesticide exposure during this time.[Greenop KR, Peters S, Bailey HD, et al. 2013. Cancer Causes Control. 24(7):1269-78]

Exposure to pesticides and risk of childhood cancer: a meta-analysis of recent epidemiological studiesThe authors performed a meta-analysis of case-control and cohort studies to clarify the possible relationship between exposure to pesticides and childhood cancers.Two cohort and 38 case-control studies were selected for the first meta-analysis.Meta-analysis of the three cohort studies did not show any positive links between parental pesticide exposure and childhood cancer incidence. However, the meta-analysis of the 40 studies with OR values showed that the risk of lymphoma and leukaemia increased significantly in exposed children when their mother was exposed during the prenatal period. The risk of brain cancer was correlated with paternal exposure either before or after birth. The OR of leukaemia and lymphoma was higher when the mother was exposed to pesticides (through household use or professional exposure). Conversely, the incidence of brain cancer was influenced by the father's exposure (occupational activity or use of household or garden pesticides). Despite some limitations in this study, the incidence of childhood cancer does appear to be associated with parental exposure during the prenatal period.[Vinson F, Merhi M, Baldi I, Raynal H, et al. 2011. Occup Environ Med. 68(9):694-702.]

Childhood brain tumors, residential insecticide exposure, and pesticide metabolism genesA population-based, case control study of California and Washington state born children ten years of age or younger and functional genetic polymorphisms and parents use of home insecticide treatments finds a strong interaction between insecticide exposure during childhood and chromosome genotype PON1-108T allele (OR 1.8) and FMO1-9536A (*6) allele (OR = 2.7), suggesting that exposure in childhood to insecticides in combination with a reduced ability to detoxify them increases risk of developing brain tumors.[Nielsen, S.S., et al. 2010. Childhood brain tumors, residential insecticide exposure, and pesticide metabolism genes. Environmental Health Perspectives 118(1):144-149]

Critical Confluence: Gene Variants, Insecticide Exposure May Increase Childhood Brain Tumor RiskEpidemiologic data have suggested a link between pesticide exposures and childhood brain tumors. The link may be specific to insecticides such as organophosphorus and carbamate compounds, which are known to target the nervous system. Previously published work investigated the role of individual genetic variation with a focus on paraoxonase (PON1), a key enzyme in the metabolism of organophosphorus insecticides commonly used in homes at the time but now banned for residential use. This work showed that children with brain tumors were more likely to carry a common single-nucelotide polymorphism (SNP) gene variant in the promoter region of the PON1 gene (PON1C-108T) than other children, and that the association between this SNP and brain tumors was stronger in children with a history of home insecticide exposure. Research in an expanded study population now provides additional evidence that exposure to insecticides, paired with specific metabolism gene variants, may increase the risk of childhood brain tumors.[Barrett, J. 2010. Environ Health Perspect. 118(1): A35]

Parental exposure to pesticides and childhood brain cancer: U.S. Atlantic coast childhood brain cancer study.The etiology of childhood brain cancer remains largely unknown. However, previous studies have yielded suggestive associations with parental pesticide use. Study aimed to evaluate parental exposure to pesticides at home and on the job in relation to the occurrence of brain cancer in children. Authors included 526 one-to-one-matched case-control pairs. Brain cancer cases were diagnosed at < 10 years of age, and were identified from statewide cancer registries of four U.S. Atlantic Coast states. Using information on residential pesticide use and jobs held by fathers during the 2-year period before the child's birth, authors assessed potential exposure to insecticides, herbicides, and fungicides. A significant risk of astrocytoma was associated with exposures to herbicides from residential use. Combining parental exposures to herbicides from both residential and occupational sources, the elevated risk remained significant. However, these findings should be viewed in light of limitations in exposure assessment and effective sample size.[Shim YK, Mlynarek SP, van Wijngaarden E. 2009.Environ Health Perspect. 117(6):1002-6.]

Risk of brain tumors in children and susceptibility to organophosphorus insecticides: the potential role of paraoxonase (PON1).Prior research suggests that childhood brain tumors (CBTs) may be associated with exposure to pesticides. Organophosphorus insecticides (OPs) target the developing nervous system, and until recently, the most common residential insecticides were chlorpyrifos and diazinon, two OPs metabolized in the body through the cytochrome P450/paraoxonase 1 (PON1) pathway. To investigate whether two common PON1 polymorphisms, C-108T and Q192R, are associated with CBT occurrence, authors conducted a population-based study of 66 cases and 236 controls using DNA from neonatal screening archive specimens in Washington State, linked to interview data. The risk of CBT was nonsignificantly increased in relation to the inefficient PON1 promoter allele [per PON1(-108T) allele, relative to PON1(-108CC): odds ratio (OR) = 1.4; 95% confidence interval (CI), 1.0-2.2; p-value for trend = 0.07]. Notably, this association was strongest and statistically significant among children whose mothers reported chemical treatment of the home for pests during pregnancy or childhood (per PON1(-108T) allele: among exposed, OR = 2.6; 95% CI, 1.2-5.5; among unexposed, OR = 0.9; 95% CI, 0.5-1.6) and for primitive neuroectodermal tumors (per PON1(-108T) allele: OR = 2.4; 95% CI, 1.1-5.4). Larger studies that measure plasma PON1 levels and incorporate more accurate estimates of pesticide exposure will be required to confirm these observations.[Searles Nielsen S, Mueller BA, De Roos AJ, et al. 2005. Environ Health Perspect.113(7):909-13.]

Household pesticides and risk of pediatric brain tumorsPrenatal exposure to flea and tick pesticides significantly increased the risk for pediatric brain tumor, especially for children less than five years old at diagnosis. Prenantal risk is highest for mothers who prepared, applied, or cleaned up the products themselves. Sprays and fogger flea and tick products showed the most significant risk.[Pogoda, J.M. and Preston-Martin, S. 1997. Environmental Health Perspectives 105:1214-1220]

Family pesticide use and childhood brain cancer.Studies show that children living in households where pesticides are used suffer elevated rates of brain cancer, for some age and pesticide specific exposures.[Davis, J., et al. 1993. Family pesticide use and childhood brain cancer. Archives of Environmental Contamination and Toxicology 24:87-92]

Risk factors for brain tumors in childrenAn exploratory case-control study in Baltimore, Maryland finds that more children with brain tumors and children with other cancers are found to have been exposed to insecticides than other children.[Gold, E., et al. 1979. American Journal of Epidemiology 109(3):309-319]

Adult Brain Cancer

Occupational exposure to pesticides and risk of adult brain tumors.A hospital-based case-control study finds that woman with occupational herbicide exposure show an increased risk meningioma compared to woman who never used herbicides (OR 2.4), a significant trend for increasing risk with increasing years of herbicide exposure and increasing cumulative exposure.[Samanic, C.M., et al. 2008. American Journal of Epidemiology 167(8):976-985]

Brain tumours and exposure to pesticides: a case-control study in southwestern France.A population-based case–control study in France finds that pesticides play a role in brain tumors for high levels of occupational exposures (OR 2.16), especially for gliomas (OR 3.21).[Provost, D., et al. 2007. Brain tumours and exposure to pesticides: a case-control study in southwestern France. Occupational and Environmental Medicine 64:509-514]

Agricultural pesticide use and risk of glioma in Nebraska, United StatesIn a population based case control study in eastern Nebraska, men living or working on a farm for at least 55 years is associated with an almost 4-fold increased risk of glioma . Among male farmers, the study finds an increase risk for glioma for those exposed to herbicides metribuzin and paraquat , insecticides bufencarb and chlorpyrifos and coumaphos.[Lee, W., et al. 2005. Occupational and Environmental Medicine 62(11):786-792]

Occupational Exposure to Carbofuran and the Incidence of Cancer in the Agricultural Health StudyA geographical study looking at pesticide use and cancer incidence in Costa Rica finds that in areas of mainly coffee production there are elevated number of brain cancers, particularly for men; it also found that for rural counties with heavy pesticide use there is an association with an increase risk for brain cancer in females.[Wesseling, C., et al. 1999. International Journal of Epidemiology 28: 365-374]

Breast Cancer

Comparison of Weibull and Lognormal Cure Models with Cox in the Survival Analysis Of Breast Cancer Patients in Rafsanjan.The current study retrospective cohort study was conducted on 140 patients referred to Ali Ibn Abitaleb Hospital, Rafsanjan southeastern Iran from 2001 to 2015 suffering from breast cancer. According to AIC, log-normal model was more consistent than Weibull. In the multivariable Lognormal model, the effective factors like smoking, second -hand smoking, drinking herbal tea and the last breast-feeding period were included. In addition, using Cox regression factors of significant were the disease grade, size of tumor and its metastasis (p-value<0.05). As Rafsanjan is surrounded by pistachio orchards and pesticides applied by farmers, people of this city are exposed to agricultural pesticides and its harmful consequences. The effect of the pesticide on breast cancer was studied and the results showed that the effect of pesticides on breast cancer was not in agreement with the models used in this study. Based on different methods for survival analysis, researchers can decide how they can reach a better conclusion. This comparison indicates the result of semi-parametric Cox method is closer to clinical experiences evidences.[Hoseini M, Bahrampour A, Mirzaee M. 2017. J Res Health Sci. 17(1):E1-6.]

Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents.The safety, including the endocrine disruptive capability, of glyphosate-based herbicides (GBHs) is a matter of intense debate. Authors evaluated the estrogenic potential of glyphosate, commercial GBHs and polyethoxylated tallowamine adjuvants present as co-formulants in GBHs. Glyphosate (≥10,000 μg/L or 59 μM) promoted proliferation of estrogen-dependent MCF-7 human breast cancer cells. Glyphosate also increased the expression of an estrogen response element-luciferase reporter gene (ERE-luc) in T47D-KBluc cells, which was blocked by the estrogen antagonist ICI 182,780. Commercial GBH formulations or their adjuvants alone did not exhibit estrogenic effects in either assay. Transcriptomics analysis of MCF-7 cells treated with glyphosate revealed changes in gene expression reflective of hormone-induced cell proliferation but did not overlap with an ERα gene expression biomarker. Calculation of glyphosate binding energy to ERα predicts a weak and unstable interaction (-4.10 kcal mol-1) compared to estradiol (-25.79 kcal mol-1), which suggests that activation of this receptor by glyphosate is via a ligand-independent mechanism. Induction of ERE-luc expression by the PKA signalling activator IBMX shows that ERE-luc is responsive to ligand-independent activation, suggesting a possible mechanism of glyphosate-mediated activation. Study reveals that glyphosate, but not other components present in GBHs, can activate ERα in vitro, albeit at relatively high concentrations.[Mesnage R, Phedonos A, Biserni M, et al. 2017. Food Chem Toxicol. 108(Pt A):30-42.]

Levels of persistent organic pollutants in breast milk of Maya women in Yucatan, Mexico.In this study, 24 breast milk samples, obtained from rural Maya women, from municipalities of Yucatan, Mexico, were analyzed for organochlorine pesticide (OCP) residues by gas chromatography. Recent studies have shown that Maya communities have a poor perception about the proper usage and handling of OCP. The karstic soil in this area has a high vulnerability to groundwater pollution by the use of OCP in agriculture and livestock activities. The impact of the ecosystem on human health is much more critical due to the prevailing poverty and a very low educational level of these communities. About 30% of the Maya population consumes water directly from contaminated wells and sinkholes, resulting in a chronic exposure to OCP. The samples served to identify and quantify high levels of OCP residues (18.43 mg/kg of heptachlor epoxide and 1.92 mg/kg of endrin in the metropolitan zone; 2.10 mg/kg of dieldrin, 0.117 mg/kg of endosulfan II, 0.103 mg/kg of heptachlor, 0.178 mg/kg of endrin, and 0.127 mg/kg of endrin aldehyde in the main agricultural zone and on the west coast). The detected levels of OCP residues are a major concern and represent a potential risk to women and children in the region. This could be associated with the high rates of cervical uterine and breast cancer mortality in Yucatan. Thus, regulations on the usage of OCP and their enforcement are necessary, and it is important to establish a yearly monitoring program for OCP residues in breast milk and groundwater, as well as to implement health promotion programs for women in particular and the general population in general.[Polanco Rodríguez ÁG, Inmaculada Riba López M, Angel DelValls Casillas T, et al. Environ Monit Assess.189(2):59. ]

Levels of persistent organic pollutants in breast milk of Maya women in Yucatan, Mexico.In this study, 24 breast milk samples, obtained from rural Maya women, from municipalities of Yucatan, Mexico, were analyzed for organochlorine pesticide (OCP) residues by gas chromatography. Recent studies have shown that Maya communities have a poor perception about the proper usage and handling of OCP. The karstic soil in this area has a high vulnerability to groundwater pollution by the use of OCP in agriculture and livestock activities. The impact of the ecosystem on human health is much more critical due to the prevailing poverty and a very low educational level of these communities. About 30% of the Maya population consumes water directly from contaminated wells and sinkholes, resulting in a chronic exposure to OCP. The samples served to identify and quantify high levels of OCP residues (18.43 mg/kg of heptachlor epoxide and 1.92 mg/kg of endrin in the metropolitan zone; 2.10 mg/kg of dieldrin, 0.117 mg/kg of endosulfan II, 0.103 mg/kg of heptachlor, 0.178 mg/kg of endrin, and 0.127 mg/kg of endrin aldehyde in the main agricultural zone and on the west coast). The detected levels of OCP residues are a major concern and represent a potential risk to women and children in the region. This could be associated with the high rates of cervical uterine and breast cancer mortality in Yucatan. Thus, regulations on the usage of OCP and their enforcement are necessary, and it is important to establish a yearly monitoring program for OCP residues in breast milk and groundwater, as well as to implement health promotion programs for women in particular and the general population in general.[Polanco Rodríguez ÁG, Inmaculada Riba López M, Angel DelValls Casillas T, et al. 2017. Environ Monit Assess. 189(2):59]

Occupational exposures and genetic susceptibility to urinary tract cancers: a systematic review and meta-analysis.This study aims to summarize the current knowledge on the relationship between genetic polymorphisms, occupational exposures, and urinary tract cancers. Authors searched MEDLINE, ISI Web of science, and SCOPUS online databases for all articles published in English language up to September 2016. A meta-analysis was performed to provide summary estimates for the association between a certain genetic polymorphism, occupational exposure and bladder cancer (BC) or kidney cancer (KC), when appropriate. Fifteen studies on BC and six on KC were deemed eligible for the review. With regard to BC, an overall odds ratio (OR) of 2.07 [95% confidence interval (CI): 1.38-3.09] for those with GSTM1 and an OR of 2.07 (95% CI: 1.38-3.09) for those with GSTT1 null genotype were reported when exposed to polycyclic aromatic hydrocarbons (PAHs). NAT2 slow genotype carriers had an OR of 3.59 (95% CI: 2.62-4.93) for BC when exposed to aromatic amines and an OR of 2.07 (95% CI: 1.36-3.15) when exposed to PAHs. With regard to KC and pesticide exposure, the meta-analysis reported an OR of 4.38 (95% CI: 2.28-8.41) for GSTM1 present genotype, an OR of 2.59 (95% CI: 1.62-4.15) for GSTT1-present genotype and an OR of 6.51 (95% CI: 2.85-14.89) for combined effects of GSTM1 and GSTT1 active genotypes. This meta-analysis indicates a possible association between the variant genotypes of GSTM1, GSTT1, NAT2 and SULT1A1, occupational exposure to aromatic amines or PAHs, and development of BC. Our results suggest that polymorphisms in GSTM1 and GSTT1 genes could influence the risk for developing KC in individuals occupationally exposed to pesticides.[Stojanovic J, Milovanovic S, Pastorino R, et al. 2017. Eur J Cancer Prev. doi: 10.1097/CEJ.0000000000000364]

Organochlorine pesticides accumulation and breast cancer: A hospital-based case-control study.The aim of this study is to detect the accumulation status of organochlorine pesticides in breast cancer patients and to explore the relationship between organochlorine pesticides contamination and breast cancer development. A hospital-based case-control study in 56 patients with breast cancer and 46 patients with benign breast disease was conducted. The accumulation level of several organochlorine pesticides products (β-hexachlorocyclohexane, γ-hexachlorocyclohexane, polychlorinated biphenyls-28, polychlorinated biphenyls-52, pentachlorothioanisole, and pp'-dichlorodiphenyldichloroethane) in breast adipose tissues of all 102 patients was detected. Thereafter, authors examined the expression status of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER2), and Ki-67 in 56 breast cancer cases by immunohistochemistry. In addition, they analyzed the risk of breast cancer in those patients with organochlorine pesticides contamination using a logistic regression model. Data showed that breast cancer patients suffered high accumulation levels of pp'-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52. However, the concentrations of pp'-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52 were not related to clinicopathologic parameters of breast cancer. Further logistic regression analysis showed polychlorinated biphenyls-52 and pp'-dichlorodiphenyldichloroethane were risk factors for breast cancer. Results provide new evidence on etiology of breast cancer.[He TT, Zuo AJ, Wang JG, Zhao P. 2017. Tumour Biol. 39(5):1010428317699114]

Recent advances on bisphenol-A and endocrine disruptor effects on human prostate cancerEndocrine disrupting chemicals (EDCs) are man-made substances widespread in the environment that include, among many others, bisphenol A (BPA), organochlorinated pesticides and hormone derivatives detectable in meat from animals raised in concentrated animal feeding operations. Increasing evidence indicates that EDCs have a negative impact on human health as well as on male and female fertility. They may also be associated with some endocrine diseases and increased incidence of breast and prostate cancer. This review aims to summarize available data on the (potential) impact of some common EDCs, focusing particularly on BPA, prostate cancer and their mechanisms of action. These compounds interfere with normal hormone signal pathway transduction, resulting in prolonged exposure of receptors to stimuli or interference with cellular hormone signaling in target cells. Understanding the effects of BPA and other EDCs as well as their molecular mechanism(s) may be useful in sensitizing the scientific community and the manufacturing industry to the importance of finding alternatives to their indiscriminate use.[Di Donato M, Cernera G, Giovannelli P, et al. 2017. Mol Cell Endocrinol. pii: S0303-7207(17)30158-2. ]

Serum levels of environmental pollutants is a risk factor for breast cancer in Inuit: a case control study.The association between POPs and breast cancer has been widely studied but the conclusions are inconsistent. The present study examined the associations between serum levels of Persistent Organic Pollutants (POPs) and breast cancer with focus on the highly exposed Greenlandic Inuit population.The study design was a case-control study of Inuit women from Greenland. The participants were asked to complete a questionnaire with information on reproductive history and lifestyle and to provide a blood sample. The sampling was carried out in two time periods (2000-2003 and 2011-2014). The serum levels were determined of 14 polychlorinated biphenyls (PCBs), 11 organochlorine pesticides (OCPs), 16 perfluoroalkyl acids (PFAAs), 1 polybrominated biphenyl (PBB), and 9 polybrominated diphenyl ethers (PBDEs).The study population included 77 breast cancer cases and 84 controls. The majority of the measured compounds declined significantly from 2000 - 2003 to 2011-2014. However, for the perfluorinated carboxylic acids (PFCAs) an increase was observed. The serum levels were significantly higher in cases compared to controls for the majority of the compounds, and after adjusting for age the difference. For the lipophilic POPs, high serum levels (middel/highest vs. lowest tertile) were associated with breast cancer risk; for the amphiphilic PFAAs, high serum levels of ∑PFAA, ∑PFCA, ∑PFSA, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), PFHxS, and PFOS were associated with breast cancer risk. Significant, positive associations between breast cancer risk and PCBs and PFAAs were observed. The associations indicate that environmental exposure to POPs can be a factor increasing the risk for breast cancer in Inuit women.[Wielsøe M, Kern P, Bonefeld-Jørgensen EC. 2017. Environ Health. 16(1):56. ]

Childhood and Adolescent Pesticide Exposure and Breast Cancer Risk.To date, epidemiologic studies have not strongly supported an association between pesticide exposure and breast cancer. However, few previous studies had the ability to assess specific time periods of exposure. Studies that relied on adult serum levels of metabolites of organochlorine pesticides may not accurately reflect exposure during developmental periods. Furthermore, exposure assessment often occurred after diagnosis and key tumor characteristics, such as hormone receptor status, have rarely been available to evaluate tumor subtype-specific associations. We examined the association between pesticide exposure during childhood and adolescence and breast cancer risk in the prospective Sister Study cohort (N = 50,884 women) to assess this relation by tumor subtype.During an average 5-year follow-up, 2,134 incident invasive and in situ breast cancer diagnoses were identified. Residential and farm exposure to pesticides were self-reported at study enrollment during standardized interviews. Multivariable hazard ratios and 95% confidence intervals for breast cancer risk were calculated with Cox proportional hazards regression. HRs were near null for the association between childhood/adolescent pesticide exposure and breast cancer risk overall or among ER+/PR+ invasive tumors. However, among women who were ages 0-18 before the ban of dichlordiphenyltrichloroethane in the US, exposure to fogger trucks or planes was associated with a hazard ratio = 1.3 for premenopausal breast cancer (95% confidence interval: 0.92, 1.7).These findings do not support an overall association between childhood and adolescent pesticide exposure and breast cancer risk. However, modest increases in breast cancer risk were associated with acute events in a subgroup of young women.[Niehoff NM, Nichols HB, White AJ, 2016. Epidemiology. 27(3):326-33. ]

Correlation between toxic organochlorine pesticides and breast cancer.Organochlorines (OCs) are common environmental pollutants that have been linked to cancer. This work aims to assess the role of OCs as a risk factor for breast cancer and to evaluate the cellular changes induced by exposure to such environmental contaminants. The study included 70 cancer patients subjected to thorough history taking and routine investigations. Samples from tumor and normal adjacent tissue were taken to measure OCs' levels and to perform molecular analysis (some oncogenic and apoptotic markers) by flow cytometry. There were significantly higher concentrations of methoxychlor, dichloro-diphenyl-trichloroethane (DDT), hexa-chlorobenzene (HCB), and chlordane in tumor tissue samples compared to the surrounding normal tissue. There was a positive statistically significant correlation between G2m and dichloro-diphenyl-dichloroethane, DDT, and methoxychlor. There was also a negative correlation between propidium iodide (PI) and heptachlor as well as between PI, B-cell lymphoma 2, and methoxychlor. Annexin showed a negative correlation with HCB and methoxychlor. In conclusion, the higher level of organochlorine pesticides in the tissue specimens of breast cancer and the resultant molecular dysfunction highlight a possible association. Further research is warranted to elucidate the other possible mechanisms involved in the process of carcinogenesis.[Eldakroory SA, Morsi DE, Abdel-Rahman RH, et al. 2016. Hum Exp Toxicol.:960327116685887]

Correlation between toxic organochlorine pesticides and breast cancer.Organochlorines (OCs) are common environmental pollutants that have been linked to cancer. This work aims to assess the role of OCs as a risk factor for breast cancer and to evaluate the cellular changes induced by exposure to such environmental contaminants. The study included 70 cancer patients subjected to thorough history taking and routine investigations. Samples from tumor and normal adjacent tissue were taken to measure OCs' levels and to perform molecular analysis (some oncogenic and apoptotic markers) by flow cytometry. There were significantly higher concentrations of methoxychlor, dichloro-diphenyl-trichloroethane (DDT), hexa-chlorobenzene (HCB), and chlordane in tumor tissue samples compared to the surrounding normal tissue. There was a positive statistically significant correlation between G2m and dichloro-diphenyl-dichloroethane, DDT, and methoxychlor. There was also a negative correlation between propidium iodide (PI) and heptachlor as well as between PI, B-cell lymphoma 2, and methoxychlor. Annexin showed a negative correlation with HCB and methoxychlor. In conclusion, the higher level of organochlorine pesticides in the tissue specimens of breast cancer and the resultant molecular dysfunction highlight a possible association. Further research is warranted to elucidate the other possible mechanisms involved in the process of carcinogenesis.[Eldakroory SA, Morsi DE, Abdel-Rahman RH, et al. 2016. Hum Exp Toxicol. 960327116685887]

Differences in GPR30 Regulation by Chlorotriazine Herbicides in Human Breast CellsOver 200,000 cases of invasive breast cancer are diagnosed annually; herbicide contaminants in local water sources may contribute to the growth of these cancers. GPR30, a G protein coupled receptor, was identified as a potential orphan receptor that may interact with triazine herbicides such as atrazine, one of the most commonly utilized chlorotriazines in agricultural practices in the United States. Our goal was to identify whether chlorotriazines affected the expression of GPR30. Two breast cancer cell lines, MDA-MB-231 and MCF-7, as well as one normal breast cell line, MCF-10A, were treated with a 100-fold range of atrazine, cyanazine, or simazine, with levels flanking the EPA safe level for each compound. Using real-time PCR, we assessed changes in GPR30 mRNA compared to a GAPDH control. Our results indicate that GPR30 expression increased in breast cancer cells at levels lower than the US EPA drinking water contamination limit. During this treatment, the viability of cells was unaltered. In contrast, treatment with chlorotriazines reduced the expression of GPR30 in noncancerous MCF-10A cells. Thus, our results indicate that cell milieu and potential to metastasize may play a role in the extent of GPR30 response to pesticide exposure.[Florian CP, Mansfield SR, Schroeder JR. Biochem Res Int. 2016:2984081]

Differential gene expression pattern in human mammary epithelial cells induced by realistic organochlorine mixtures described in healthy women and in women diagnosed with breast cancer.Organochlorine pesticides (OCs) have been associated with breast cancer development and progression, but the mechanisms underlying this phenomenon are not well known. In this work, we evaluated the effects exerted on normal human mammary epithelial cells (HMEC) by the OC mixtures most frequently detected in healthy women (H-mixture) and in women diagnosed with breast cancer (BC-mixture), as identified in a previous case-control study developed in Spain. Cytotoxicity and gene expression profile of human kinases (n=68) and non-kinases (n=26) were tested at concentrations similar to those described in the serum of those cases and controls. Although both mixtures caused a down-regulation of genes involved in the ATP binding process, our results clearly indicate that both mixtures may exert a very different effect on the gene expression profile of HMEC. Thus, while BC-mixture up-regulated the expression of oncogenes associated to breast cancer (GFRA1 and BHLHB8), the H-mixture down-regulated the expression of tumor suppressor genes (EPHA4 and EPHB2). Our results indicate that the composition of the OC mixture could play a role in the initiation processes of breast cancer. In addition, the present results suggest that subtle changes in the composition and levels of pollutants involved in environmentally relevant mixtures might induce very different biological effects, which explain, at least partially, why some mixtures seem to be more carcinogenic than others. Nonetheless, our findings confirm that environmentally relevant pollutants may modulate the expression of genes closely related to carcinogenic processes in the breast, reinforcing the role exerted by environment in the regulation of genes involved in breast carcinogenesis.[Rivero J, Henríquez-Hernández LA, Luzardo OP, et al. Toxicol Lett. 246:42-8. ]

Epidemiological trends of hormone-related cancers in Slovenia.The incidence of hormone-related cancers tends to be higher in the developed world than in other countries. In Slovenia, six hormone-related cancers (breast, ovarian, endometrial, prostate, testicular, and thyroid) account for a quarter of all cancers. Their incidence goes up each year, breast and prostate cancer in particular. The age at diagnosis is not decreasing for any of the analysed cancer types. The risk of breast cancer is higher in the western part of the country, but no differences in geographical distribution have been observed for other hormone-related cancers. Furthermore, areas polluted with endocrine-disrupting chemicals that affect hormone balance such as PCBs, dioxins, heavy metals, and pesticides, do not seem to involve a greater cancer risk. We know little about how many cancers can be associated with endocrine disruptors, as there are too few reliable exposure studies to support an association.[Zadnik V, Krajc M. Arh Hig Rada Toksikol. 67(2):83-92. ]

Epidemiological trends of hormone-related cancers in Slovenia.The incidence of hormone-related cancers tends to be higher in the developed world than in other countries. In Slovenia, six hormone-related cancers (breast, ovarian, endometrial, prostate, testicular, and thyroid) account for a quarter of all cancers. Their incidence goes up each year, breast and prostate cancer in particular. The age at diagnosis is not decreasing for any of the analysed cancer types. The risk of breast cancer is higher in the western part of the country, but no differences in geographical distribution have been observed for other hormone-related cancers. Furthermore, areas polluted with endocrine-disrupting chemicals that affect hormone balance such as PCBs, dioxins, heavy metals, and pesticides, do not seem to involve a greater cancer risk. We know little about how many cancers can be associated with endocrine disruptors, as there are too few reliable exposure studies to support an association.[Zadnik V, Krajc M. 2016. Arh Hig Rada Toksikol. 67(2):83-92. ]

Human exposure to endocrine disrupting compounds: Their role in reproductive systems, metabolic syndrome and breast cancer. A review
Endocrine disrupting chemicals (EDCs) are released into the environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDCs have major risks for humans by targeting different organs and systems in the body (e.g. reproductive system, breast tissue, adipose tissue, pancreas, etc.). Due to the ubiquity of human exposure to these compounds the aim of this review is to describe the most recent data on the effects induced by phthalates, bisphenol A and parabens in a critical window of exposure: in utero, during pregnancy, infants, and children. The interactions and mechanisms of toxicity of EDCs in relation to human general health problems, especially those broadening the term of endocrine disruption to 'metabolic disruption', should be deeply investigated. These include endocrine disturbances, with particular reference to reproductive problems and breast, testicular and ovarian cancers, and metabolic diseases such as obesity or diabetes.[Giulivo M, Lopez de Alda M, Capri E, Barceló D. 2016. Environ Res. 151:251-264.]

Occupational exposure and risk of breast cancerBreast cancer is a multifactorial disease and the most commonly diagnosed cancer in women. Traditional risk factors for breast cancer include reproductive status, genetic mutations, family history and lifestyle. However, increasing evidence has identified an association between breast cancer and occupational factors, including environmental stimuli. Epidemiological and experimental studies demonstrated that ionizing and non-ionizing radiation exposure, night-shift work, pesticides, polycyclic aromatic hydrocarbons and metals are defined environmental factors for breast cancer, particularly at young ages. However, the mechanisms by which occupational factors can promote breast cancer initiation and progression remains to be elucidated. Furthermore, the evaluation of occupational factors for breast cancer, particularly in the workplace, also remains to be explained. The present review summarizes the occupational risk factors and the associated mechanisms involved in breast cancer development, in order to highlight new environmental exposures that could be correlated to breast cancer and to provide new insights for breast cancer prevention in the occupational settings. Furthermore, this review suggests that there is a requirement to include, through multidisciplinary approaches, different occupational exposure risks among those associated with breast cancer development. Finally, the design of new epigenetic biomarkers may be useful to identify the workers that are more susceptible to develop breast cancer.[Fenga C. Biomed Rep. 4(3):282-292.]

Chlorpyrifos inhibits cell proliferation through ERK1/2 phosphorylation in breast cancer cell lines.It has been reported that oxidative stress may be induced by pesticides and it could be the cause of health alteration mediated by pollutants exposure. The present investigation was designed to identify the pathway involved in chlorpyrifos (CPF)-inhibited cell proliferation in MCF-7 and MDA-MB-231 breast cancer cell lines. In addition, authors determined if CPF-induced oxidative stress is related to alterations in antioxidant defense system. The molecular mechanisms underlying in the cell proliferation inhibition produced by the pesticide were also looked at. Study demonstrates that CPF (50 μM) induces redox imbalance altering the antioxidant defense system in breast cancer cells. The main mechanism involved in the inhibition of cell proliferation induced by CPF is an increment of p-ERK1/2 levels mediated by H2O2 in breast cancer cells. Study concluded that ERK1/2 phosphorylation is subsequent to ROS production induced by CPF but not the inverse.[Ventura C, Venturino A, Miret N, et al. 2015. Chemosphere. 120:343-50.]

Effects of environmental organochlorine pesticides on human breast cancer: putative involvement on invasive cell abilityPOPs are known to be particularly toxic and have been associated with endocrine-disrupting effects in several mammals, including humans even at very low doses. As environmental estrogens, they could play a critical role in carcinogenesis, such as in breast cancer. With the purpose of evaluating their effect on breast cancer biology, o,p'-DDT, p,p'-DDE, and p,p'-DDD (50-1000 nM) were tested on two human breast adenocarcinoma cell lines: MCF-7 expressing estrogen receptor (ER) α and MDA-MB-231 negative for ERα, regarding cell proliferation and viability in addition to their invasive potential. Cell proliferation and viability were not equally affected by these compounds. In MCF-7 cells, the compounds were able to decrease cell proliferation and viability. On the other hand, no evident response was observed in treated MDA-MB-231 cells. Concerning the invasive potential, the less invasive cell line, MCF-7, had its invasion potential significantly induced, while the more invasive cell line MDA-MB-231, had its invasion potential dramatically reduced in the presence of the tested compounds. Altogether, the results showed that these compounds were able to modulate several cancer-related processes, namely in breast cancer cell lines, and underline the relevance of POP exposure to the risk of cancer development and progression, unraveling distinct pathways of action of these compounds on tumor cell biology.[Pestana D, Teixeira D, Faria A, Domingues V, et al. 2015. Environ Toxicol. 30(2):168-76.]

In vitro evaluation of oestrogenic/androgenic activity of the serum organochlorine pesticide mixtures previously described in a breast cancer case-control study.Some organochlorine pesticides (OCs) have been individually linked to breast cancer (BC) because they exert oestrogenic effects on mammary cells. In this work authors evaluated the in vitro effects exerted on human BC cells by the OC mixtures that were most frequently detected in two groups of women who participated in a BC case-control study developed in Spain: healthy women and women diagnosed with BC. The cytotoxicity, oestrogenicity, and androgenicity of the most prevalent OC mixtures found in healthy women (H-mixture) and in BC patients (BC-mixture) were tested at concentrations that resembled those found in the serum of the evaluated women. Our results showed that both OC mixtures presented a similar oestrogenic activity and effect on cell viability, but BC-mixture showed an additional anti-androgenic effect. These results indicate that although the proliferative effect exerted by these mixtures on human breast cells seems to depend mainly on their oestrogenic action, the BC-mixture might additionally induce cell proliferation due to its anti-androgenic activity, therefore increasing the carcinogenic potential of this mixture. The findings of this study demonstrate that subtle variations in the composition of a mixture may induce relevant changes in its biological action.[Rivero J, Luzardo OP, Henríquez-Hernández LA, Machín RP, et al. 2015. Sci Total Environ. 537:197-202]

Organochlorine insecticides DDT and chlordane in relation to survival following breast cancer.Study examined associations between organochlorine insecticides p,p'-DDT , its primary metabolite, p,p'-DDE, and chlordane assessed shortly after diagnosis and survival among women with breast cancer. A population-based sample of women diagnosed with a first primary invasive or in situ breast cancer in 1996-1997 and with available organochlorine blood measures (n = 633) were followed for vital status through 2011. After follow-up of 5 and 15 years, authors identified 55 and 189 deaths, of which 36 and 74, respectively, were breast cancer-related. At 5 years after diagnosis, the highest tertile of DDT concentration was associated with all-cause (HR = 2.19; 95% CI: 1.02, 4.67) and breast cancer-specific (HR = 2.72; 95% CI: 1.04, 7.13) mortality. At 15 years, middle tertile concentrations of DDT (HR = 1.42; 95% CI 0.99, 2.06) and chlordane (HR = 1.42; 95% CI: 0.94, 2.12) were modestly associated with all-cause and breast cancer-specific mortality. Third tertile DDE concentrations were inversely associated with 15-year all-cause mortality (HR = 0.66; 95% CI: 0.44, 0.99). This is the first population-based study in the United States to show that DDT may adversely impact survival following breast cancer diagnosis. Further studies are warranted given the high breast cancer burden and the ubiquity of these chemicals.[Parada H Jr, Wolff MS, Engel LS, White AJ, et al. 2015. Int J Cancer. doi: 10.1002/ijc.29806]

Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health StudyOrganophosphates (OPs) are among the most commonly used insecticides. OPs have been linked to cancer risk in some epidemiological studies, which have been largely conducted in predominantly male populations. This study evaluated personal use of specific OPs and cancer incidence among female spouses of pesticide applicators in the prospective Agricultural Health Study cohort. Among 30 003 women, 25.9% reported OP use, and 718 OP-exposed women were diagnosed with cancer during the follow-up period. Any OP use was associated with an elevated risk of breast cancer (RR=1.20, 95% CI 1.01 to 1.43). Malathion, the most commonly reported OP, was associated with increased risk of thyroid cancer (RR=2.04, 95% CI 1.14 to 3.63) and decreased risk of non-Hodgkin lymphoma (RR=0.64, 95% CI 0.41 to 0.99). Diazinon use was associated with ovarian cancer (RR=1.87, 95% CI 1.02 to 3.43).Authors observed increased risk with OP use for several hormonally-related cancers, including breast, thyroid and ovary, suggesting potential for hormonally-mediated effects. This study represents the first comprehensive analysis of OP use and cancer risk among women, and thus demonstrates a need for further evaluation.[Lerro CC, Koutros S, Andreotti G, Friesen MC, et al. 2015. Occup Environ Med. 72(10):736-44]

Risk of female breast cancer and serum concentrations of organochlorine pesticides and polychlorinated biphenyls: a case-control study in TunisiaThe aim of this study was to investigate the association between serum concentrations of a group of organochlorine pesticides/polychlorinated biphenyls with xenoestrogenic potential and the risk of breast cancer in a female population from Tunisia. β-hexachlorocyclohexane (β-HCH), hexachlorobenzene, heptachlor, polychlorinated biphenyl congeners 138, 153, and 180, and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) were positively associated with breast cancer risk. However, when the models were further adjusted for the selected covariates, only β-HCH and p,p'-DDE remained statistically significant, and heptachlor was borderline significant. In addition, analyses using POP concentration tertiles corroborated a positive dose-response relationship that was significant for p,p'-DDE. A similar trend was also confirmed for β-HCH, in which concentrations≥limit of detection were positively associated with breast cancer risk (vs. concentrations<limit of detection, OR=3.44, p<0.05). Finally, the relative influence of each chemical in the presence of the others was assessed by entering the three chemicals in a single model with all covariates, and only β-HCH remained positively associated with the risk of cancer. Findings suggest a potential association between exposure to at least one organochlorine pesticide and breast cancer risk. However, our results should be interpreted with caution, and further research is warranted to confirm these findings.[Arrebola JP, Belhassen H, Artacho-Cordón F, Ghali R, Ghorbel H, et al. 2015. Sci Total Environ. 520:106-13]

The organochlorine pesticides residues in the invasive ductal breast cancer patients.75 invasive ductal carcinoma (IDC) patients were enrolled with control of 79 benign breast diseases patients and control of 80 healthy women. Morning fasting blood specimens and adipose tissue specimens beside the primary lesion were detected with gas chromatograph. In blood specimens, both levels of β-HCH and PCTA were higher in IDC than those in both controls, and increasingly higher among the three IDC degrees. In adipose tissue specimens, all levels of β-HCH, PCTA and pp'-DDE were higher in IDC than those in control (all p<0.05) and increasingly higher among three IDC degrees. The levels of β-HCH, PCTA in both blood specimens and adipose tissue specimens were higher in estrogen receptor (ER) positive IDC than those in ER negative IDC. The higher level of organochlorine pesticides residues in blood and adipose tissue specimens of IDC infers its association with IDC, but the details remains to reveal, and this study may helpful in this field.[Yang JZ, Wang ZX, Ma LH, Shen XB, et al. 2015. Environ Toxicol Pharmacol. 40(3):698-703]

Timing of Environmental Exposures as a Critical Element in Breast Cancer RiskLiterature was reviewed and evidence gathered on the effects of the environment on risk of breast cancer or mammary tumor development in animal research models as it pertained to the influence of timing of exposure on later-life outcomes.Evidence has accumulated for several chemicals that environmental factors have a stronger effect on breast cancer risk when exposure occurred early in life. The insecticide, dichlorodiphenyltrichloroethane, is an excellent example and is just one of several chemicals for which there seems to be both animal and human evidence for the developmental basis of adult disease. The developing breast undergoes many changes in early life, leaving it vulnerable to the effects of epigenetic marks, endocrine disruption, and carcinogens. More research is needed in the area of early beginnings of breast cancer, with prevention of the disease as the ultimate goal.[Fenton S and Birnbaum, L. 2015. Endocrine Soc. http://dx.doi.org/10.1210/jc.2015-2848]

Assessing the underlying breast cancer risk of Chinese females contributed by dietary intake of residual DDT from agricultural soils.The greatest concern over DDT exposure in China arose since the early 1990s for the rising breast cancer incidence, and the cause still remains to be elucidated. An extensive survey of DDT background in agricultural soils, covered the entire region of China, was conducted. Considering the geographical differences with diverse DDT contributions and different diet products and habits, the average daily dietary intake was modeled and estimated to be 0.34 μg/kg p,p'-DDE (the main bioactive constituent in DDT). Population attributable fraction derived from a case-control study from 78 women with breast cancer and 72 controls was used to assess the DDT exposure risk to breast cancer. Based on the estimated population attributable fraction with a median value of 0.6% (IQR 0.23-2.11%), the excess annual breast cancer incidence rate attributable to p,p'-DDE exposure averaged 0.06×10(-5) with significant spatial variations varying from 0.00021×10(-5) to 11.05×10(-5) in Chinese females. Exposure to DDT is a contributor to breast cancer, but the overall limited relative risk and population attributable fraction imply confounding factors for breast cancer in Chinese females.[Tang M, Zhao M, Zhou S, et al. 2014. Environ Int. 73:208-15]

Case-control study of breast cancer and exposure to synthetic environmental chemicals among Alaska Native women.Study aimed to measure the association between exposure to select environmental chemicals and breast cancer among AN women.A case-control study of 170 women (75 cases, 95 controls) were recruited from the AN Medical Center from 1999 to 2002. Serum concentrations of most pesticides and 3 indicator PCB congeners (PCB-138/158; PCB-153, PCB-180) were lower in case women than controls. Persistent pesticides, PCBs, and most phthalate metabolites were not associated with case status in univariate logistic regression. The odds of being a case were higher for those with urinary mono-(2-ethylhexyl) phthalate (MEHP) concentrations that were above the median. Women with oestrogen receptor (ER)-/progesterone receptor (PR)-tumour types tended to have higher concentrations of persistent pesticides than did ER+/PR+ women, although these differences were not statistically significant. Exposure to the parent compound of the phthalate metabolite MEHP may be associated with breast cancer.[Holmes AK, Koller KR, Kieszak SM, Sjodin A, et al. 2014. Int J Circumpolar Health. 73:25760.]

Exogenous hormonal regulation in breast cancer cells by phytoestrogens and endocrine disruptors.Observations on the role of ovarian hormones in breast cancer growth, as well as interest in contraception, stimulated research into the biology of estrogens. In this review authors discuss chemistry, structure and classification, estrogen signaling and the consequences of the interactions of estrogens, phytoestrogens and xenoestrogens with their receptors, the complex interactions of endogenous and exogenous ligands, the evaluation of the health risks related to xenoestrogens, and the perspectives toward the synthesis of potent third generation selective estrogen receptor modulators (SERMs).[Albini A, Rosano C, Angelini G, Amaro A, et al.2014. Curr Med Chem. 21(9):1129-45.]

Household and occupational exposure to pesticides and risk of breast cancer.The association between breast cancer in women and the use of household or occupational pesticides was examined in a population-based case-control study. This study was conducted in Western Australia in 2009-2011 and included 1,789 controls and 1,205 cases. Information on household pesticide exposure was collected from questionnaires. For occupational pesticide exposure, job-specific modules (JSMs) were used. Women's exposures to pesticides in households and workplaces were not related to increased risk of breast cancer. The prevalence of occupational exposure to pesticides among women in our study was low. In the stratified analyses, the odd ratios associated with household pesticide use were similar among participants who believed pesticides increased breast cancer risk and those who did not. The results of our study did not show associations between breast cancer and household or occupational exposure to pesticides.[El-Zaemey S, Heyworth J, Glass DC, 2014. Int J Environ Health Res. 24(2):91-102]

DDT/DDE and breast cancer: a meta-analysis.The biological basis for investigating dichlorodiphenyltrichloroethane (DDT) exposure and breast cancer risk stems from in vitro and animal studies indicating that DDT has estrogenic properties. The objective of this study was to update a meta-analysis from 2004 which found no association between dichlorodiphenyldichloroethylene (DDE) and breast cancer. Summary Odds Ratios (ORs) with 95% confidence intervals (CIs) were calculated for the prevalence of breast cancer in the highest versus the lowest exposed groups for DDT and DDE. Difference of means of exposure for cases versus controls was analyzed for DDT and DDE. From the 500 studies screened, 46 were included in the meta-analysis. Slightly elevated, but not statistically significant summary ORs were found for DDE. Lipid adjusted difference of means analysis found a significantly higher DDE concentration in cases versus controls. No other difference of means analysis found significant relationships. The existing information does not support the hypothesis that exposure to DDT/DDE increases the risk of breast cancer in humans.[Ingber SZ, Buser MC, Pohl HR, et al. 2013. Regul Toxicol Pharmacol. 67(3):421-33]

Glyphosate induces human breast cancer cells growth via estrogen receptors.This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study.[Thongprakaisang S, Thiantanawat A, Rangkadilok N, et al. 2013. Food Chem Toxicol.59:129-36]

Noticing pesticide spray drift from agricultural pesticide application areas and breast cancer: a case-control study.Study examined the relationship between self-reported noticing of pesticide spray drift from agricultural areas and breast cancer. A case-control study of breast cancer was conducted in Western Australia from 2009 to 2011. Awareness of pesticide spray drift from agricultural areas was assessed by a self-report of whether the participant had noticed spray drift. This analysis included 1,743 controls and 1,169 cases. Among women who reported 'ever noticed' pesticide spray drift from agricultural areas, an increased risk of breast cancer was also observed. A dose response relationship between lifetime exposure to noticing pesticide spray drift and risk of breast cancer was observed. An increased risk of breast cancer was observed among women who noticed pesticide spray drift: initially at the age of 20 or younger; at least 20 years before diagnosis; and for 10 years or more. These findings support the hypothesis that women who ever noticed spray drift or who first noticed spray drift at a younger age had increased risk of breast cancer.[El-Zaemey S, Heyworth J, Fritschi L. 2013. Aust N Z J Public Health.37(6):547-55.]

Complex organochlorine pesticide mixtures as determinant factor for breast cancer risk: a population-based case-control study in the Canary Islands (Spain)This population-based study was designed to evaluate the profile of mixtures of organochlorines detected in 103 healthy women and 121 women diagnosed with breast cancer from Gran Canaria Island, and the relation between the exposure to these compounds and breast cancer risk.The most prevalent mixture of organochlorines among healthy women was the combination of lindane and endrin, and this mixture was not detected in any affected women. Breast cancer patients presented more frequently a combination of aldrin, dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD), and this mixture was not found in any healthy woman. After adjusting for covariables, the risk of breast cancer was moderately associated with DDD (OR = 1.008, confidence interval 95% 1.001-1.015, p = 0.024).This study indicates that healthy women show a very different profile of organochlorine pesticide mixtures than breast cancer patients, suggesting that organochlorine pesticide mixtures could play a relevant role in breast cancer risk.[Boada LD, Zumbado M, Henríquez-Hernández LA, et al. 2012. Environ Health. 11:28]

In vitro effects of herbicides and insecticides on human breast cells.Authors examined the cytotoxicity of more environmentally relevant concentrations of four herbicides, acetochlor, atrazine, cyanazine, and simazine, and two insecticides, chlorpyrifos and resmethrin, in three human breast cell lines. Interestingly, cytotoxicity was not observed in the estrogen-dependent MCF-7 mammary epithelial carcinoma cells; rather increases in cell viability were seen for some of the compounds at select concentrations. These results vary greatly from what was observed in the estrogen independent MDA-MB-231 breast cancer cells and the non-cancerous MCF-10A breast cells. This gives insight into how different tumors may respond to pesticide exposure and allows us to make more accurate conclusions about the potential cytotoxicity or, at times, stimulatory actions of these pesticides.[Rich JD, Gabriel SM, Schultz-Norton JR. 2012. ISRN Toxicol. 2012:232461]

Synergistic effect of malathion and estrogen on mammary gland carcinogenesis.Breast cancer is the most frequent malignancy diagnosed in women and is a classical model of hormone-dependent malignancy. Over the past 15-20 years, epidemiological studies have pointed to an increased breast cancer risk associated with prolonged exposure to female hormones. On the other hand, environmental chemicals such as malathion, an organophosphorous pesticide used to control a wide range of sucking and chewing pests of field crops, may be involved in the etiology of breast cancers. Results indicated that estrogen alone increased average number of lobules per mm2 of rat mammary glands in comparison to control and malathion alone at 30, 124, 240 and 400 days after 5-day treatments. On the other hand, malathion alone significantly increased the number of ducts in stage of proliferation at 10-240 days after 5-day treatments. Furthermore, markers for cancer detection such as mutant p53, c-myc, c-fos and CYPs proteins were overexpressed after treatments. Atropine, an anticholinergic drug, counteracted these effects when it was combined with malathion under similar conditions. The combination of malathion and estrogen synergistically increased number of lobules and ducts per mm2 of rat mammary glands after treatments and inducing mammary cancer. It can be concluded that combination of an environmental substance such as the pesticide malathion and an endogenous substance such as estrogen can enhance the deleterious effects in human mammary glands inducing cancer and atropine is able to diminish these effects.[Calaf GM and Echiburú-Chau C. 2012. Oncol Rep. 28(2):640-6.]

Environmental Oestrogens and Breast Cancer: Evidence for Combined Involvement of Dietary, Household and Cosmetic XenoestrogensMany environmental compounds with oestrogenic activity are measurable in the human breast and oestrogen is a known factor in breast cancer development. Exposure to environmental oestrogens occurs through diet, household products and cosmetics, but concentrations of single compounds in breast tissue are generally lower than needed for assayable oestrogenic responses. Results presented here and elsewhere demonstrate that in combination, chemicals can give oestrogenic responses at lower concentrations, which suggests that in the breast, low doses of many compounds could sum to give a significant oestrogenic stimulus. Updated incidence figures show a continued disproportionate incidence of breast cancer in Britain in the upper outer quadrant of the breast which is also the region to which multiple cosmetic chemicals are applied. If exposure to complex mixtures of oestrogenic chemicals in consumer products is a factor in breast cancer development, then a strategy for breast cancer prevention could become possible.[Darbre, P and Charles, A. 2010. Anticancer Research. 30(3): 815-827]

Pesticides and breast cancer risk: a comparison between developed and developing countriesLiterature review links DDT to breat cancer in the developing world. According to the authors, there is a dearth of studies in developing countries, which cannot be made up for generalizing the results from developed countries to the developing and third world.[Shakeel MK, George PS, Jose J, Jose J, Mathew A. 2010. Asian Pac J Cancer Prev. 2010;11(1):173-80.]

Reported residential pesticide use and breast cancer risk on Long Island, New YorkA population based, case control study of Long Island, New York breast cancer cases finds an increased risk associated with: (a) lifetime residential pesticide use (OR 1.39); (b) application of lawn insecticides themselves (OR 1.56) and is higher if it is in liquid form (OR 1.77) or a combination of product type for outdoor plants (OR 1.83); (c) professional application of pesticides in a vegetable and fruit garden more than doubled (OR 2.29); and, (d) application of pesticides for insects or diseases on outdoor plants by self (OR 1.58) or by professional (OR 1.79).[Teitelbaum, S.L., et al. 2007. American Journal of Epidemiology 165(6):643-651.]

Pesticide Use and Breast Cancer Risk among Farmers’ Wives in the Agricultural Health StudyThe authors examined the association between pesticide use and breast cancer incidence among farmers’ wives in a large prospective cohort study in Iowa and North Carolina. Participants were 30,454 women with no history of breast cancer prior to cohort enrollment in 1993–1997. Through 2000, 309 incident breast cancer cases were identified via population-based cancer registries. Rate ratios were calculated for individual pesticides using Poisson regression, controlling for confounding factors. Breast cancer standardized incidence ratios were 0.87 (95% confidence interval: 0.74, 1.02) for women who reported ever applying pesticides and 1.05 (95% confidence interval: 0.89, 1.24) for women who reported never applying pesticides. There was some evidence of increased risk associated with use of 2,4,5-trichloro-phenoxypropionic acid (2,4,5-TP) and possibly use of dieldrin, captan, and 2,4,5-trichlorophenoxyacetic acid (2,4,5-TP), but small numbers of cases among those who had personally used the pesticides precluded firm conclusions. The authors found no clear association of breast cancer risk with farm size or washing of clothes worn during pesticide application, but risk was modestly elevated among women whose homes were closest to areas of pesticide application. Further follow-up of this cohort should help clarify the relation between pesticide exposure and breast cancer risk.[Engel, L, Hill, D, Hoppin, J, et al. 2005. Am. J. Epidemiol. 161 (2): 121-135.]

Breast cancer and serum organochlorine residues.The aim of this study was to compare the blood levels of total dichlorodiphenyltrichloroethane (DDT) and hexachlorobenzene (HCB) in samples collected at the time of breast cancer discovery, in order to avoid the potential consequences of body weight change (after chemotherapy or radiotherapy) on the pesticide residue levels. Blood levels of HCB and total DDT were compared in 159 women with breast cancer and 250 presumably healthy controls. Risk of breast cancer associated with organochlorine concentration was evaluated.Mean levels of total DDT and HCB were significantly higher for breast cancer patients than for controls. No differences in serum levels of total DDT or HCB were found between oestrogen receptor positive and oestrogen receptor negative patients with breast cancer.These results add to the growing evidence that certain persistent pollutants may occur in higher concentrations in blood samples from breast cancer patients than controls.[Charlier C, Albert A, Herman P, et al.2003. Occup Environ Med. 60(5):348-51.]

A population-based case-control study of farming and breast cancer in North CarolinaA population based, case control study of North Carolina female farmers finds that while farmers in general tend to have lower breast cancer risk, for those women who reported being present in fields during or shortly after a pesticide application (OR 1.8) and for those who reported not using protective clothing while applying pesticides (OR 2.0) are at increased risk for breast cancer.[Duell, E.J., et al. 2000. Epidemiology 11(5):523-531.]

Cervical Cancer

Levels of persistent organic pollutants in breast milk of Maya women in Yucatan, Mexico.In this study, 24 breast milk samples, obtained from rural Maya women, from municipalities of Yucatan, Mexico, were analyzed for organochlorine pesticide (OCP) residues by gas chromatography. Recent studies have shown that Maya communities have a poor perception about the proper usage and handling of OCP. The karstic soil in this area has a high vulnerability to groundwater pollution by the use of OCP in agriculture and livestock activities. The impact of the ecosystem on human health is much more critical due to the prevailing poverty and a very low educational level of these communities. About 30% of the Maya population consumes water directly from contaminated wells and sinkholes, resulting in a chronic exposure to OCP. The samples served to identify and quantify high levels of OCP residues (18.43 mg/kg of heptachlor epoxide and 1.92 mg/kg of endrin in the metropolitan zone; 2.10 mg/kg of dieldrin, 0.117 mg/kg of endosulfan II, 0.103 mg/kg of heptachlor, 0.178 mg/kg of endrin, and 0.127 mg/kg of endrin aldehyde in the main agricultural zone and on the west coast). The detected levels of OCP residues are a major concern and represent a potential risk to women and children in the region. This could be associated with the high rates of cervical uterine and breast cancer mortality in Yucatan. Thus, regulations on the usage of OCP and their enforcement are necessary, and it is important to establish a yearly monitoring program for OCP residues in breast milk and groundwater, as well as to implement health promotion programs for women in particular and the general population in general.[Polanco Rodríguez ÁG, Inmaculada Riba López M, Angel DelValls Casillas T, et al. Environ Monit Assess.189(2):59. ]

Colorectal Cancer

Use of acetochlor and cancer incidence in the Agricultural Health StudyStudy evaluated the use of acetochlor and cancer incidence among licensed pesticide applicators in the Agricultural Health Study. Among 33,484 men, there were 4,026 applicators who used acetochlor and 3,234 incident cancers, with 304 acetochlor-exposed cases. Increased risk of lung cancer was observed among acetochlor users compared to nonusers, and among individuals who reported using acetochlor/atrazine product mixtures, compared to nonusers of acetochlor. Colorectal cancer risk was significantly elevated among the highest category of acetochlor users compared to never users. However the lack of exposure-response trends, small number of exposed cases and relatively short time between acetochlor use and cancer development prohibit definitive conclusions.[Lerro CC, Koutros S, Andreotti G, Hines CJ, et al. 2015. Int J Cancer.doi: 10.1002/ijc.29416.]

Cancer risk among farmers in the Province of Vercelli (Italy) from 2002 to 2005: an ecological studyFarmers living in the Province of Vercelli (Italy) were observed to verify if they have a higher cancer risk than the rest of the local employed population. The present ecological study considered all cancer new cases recorded among the mean employed population with a range of age from 25 to 84 years and resident in the Province of Vercelli during the four-year period 2002-2005. Farmers showed a higher risk for the following tumors: colorectal (OR 2.38, IC95%: 1,76-2,87), leaukaemia (OR 2.65, IC95%:2,12-2,89), digestive system (OR 2.16, IC95% 1,92-2,33), and others. Farmers showed a higher risk for several cancers. Further studies are needed, in order to examine in detail the issue, to encourage the use of personal protective equipment and to promote a more responsible pesticides use.[Salerno C, Sacco S, Panella M, et al.2014. Ann Ig. 26(3):255-63.]

A weight-of-evidence review of colorectal cancer in pesticide applicators: the agricultural health study and other epidemiologic studies.The study aimed to systematically evaluate epidemiologic studies on pesticides and colon cancer and rectal cancer in agricultural pesticide applicator populations using a transparent "weight-of-evidence" (WOE) methodological approach. Twenty-nine (29) publications from the Agricultural Health Study (AHS) and 13 additional epidemiologic studies were identified that reported data for pesticide applicators and/or specific pesticide compounds and colorectal, colon, or rectal cancer. Occupation as a pesticide applicator or pesticide application as a farming-related function was not associated with increasing the risk of colon or rectal cancer. Only aldicarb and colon cancer and imazethapyr and proximal colon cancer-appears warrant further discussion regarding a possible causal relationship, although the epidemiologic data are limited. For the remainder, a lack of a clear dose-response trend, inconsistencies in associations between exposure metrics and comparison groups, imprecise associations, variable participation rates for analyses of specific compounds, and the reliance upon data from one study (the AHS) limit interpretation regarding risk.[Alexander DD, Weed DL, Mink PJ, Mitchell ME. 2012. Int Arch Occup Environ Health. 85(7):715-45.]

Lifestyle, occupational, and reproductive factors and risk of colorectal cancerLifestyle factors and environmental exposures might help explain the risk of colorectal carcinoma in countries where the incidence is low, but unique patterns of young onset and a high proportion of rectal cancer exist. Authors obtained detailed lifestyle information from 421 patients with colorectal cancer and 439 hospital-controls in Egypt. A history of pesticide exposure and more frequently eating food directly from farms were significantly associated with a higher risk of colorectal carcinoma (odds ratio = 2.6 and odds ratio = 4.6 respectively). Parous women who reported 7 or more live births or breastfed for 19 months or longer per live birth had a significantly lower risk for colorectal carcinoma. Compared with patients aged 40 years or older, industrial exposures were more common in younger patients. Agricultural and industrial exposures were associated with increased risk of colorectal carcinoma, whereas prolonged lactation and increased parity were inversely associated with colorectal carcinoma in women. Further research to elucidate the biological role of intense environmental and industrial exposures and reproductive factors including lactation may further clarify the etiology of colorectal cancer.[Lo AC, Soliman AS, Khaled HM, et al. 2010. Dis Colon Rectum. 53(5):830-7.]

Eye Cancer

A case-control study of paternal occupational exposures and the risk of childhood sporadic bilateral retinoblastoma.The risk factors for sporadic (ie, non-familial) retinoblastoma remain largely unknown. Authors examined the relationship between paternal occupational exposures from jobs held 10 years and 1 year prior to conception and the risk of sporadic bilateral retinoblastoma in children.Paternal occupational data were obtained for 198 incident cases diagnosed with sporadic bilateral retinoblastoma from January 1998 to May 2006 and 245 referral-based controls from the case child's relatives and friends who were matched to 135 of the cases on birth year. There was some indication of an elevated risk associated with paternal pesticide exposure in the 10 years prior to conception as well as in the year before conception. However, results for pesticide exposure were inconsistent and varied by analysis approach. Exposure-response trends were observed for pesticides and non-welding metal exposures. Findings suggest a potential role of paternal occupational exposures to non-welding metals and perhaps pesticides in the aetiology of childhood retinoblastoma.[Abdolahi A, van Wijngaarden E, McClean MD, et al. 2013. Occup Environ Med. 70(6):372-9]

Gallbladder Cancer

The association of cancer risks with pentachlorophenol exposure: Focusing on community population in the areas along certain section of Yangtze River in China.Pentachlorophenol (PCP) was used in large quantities, and mainly for killing the intermediate host snails of schistosome in China, thereby resulting in ubiquitous PCP residue in the environment. However, studies considering the carcinogenicity of PCP for humans mainly focused on occupational workers, and the actual carcinogenicity of PCP for general population is uncertain. To investigate the association between cancer risks and PCP exposure in a community population, an ecological study was conducted in three contaminated areas along the Yangtze River. Standardized rate ratio (SRR) was calculated to represent the risk of cancer incidence, by using incidence in the low PCP exposure category as the reference group. A total of 15,962 cancer records were collected, and 76 water samples and 213 urine samples in three areas were examined. Findings suggested that compared with the low PCP group, the high PCP group had significantly excessive incidences of various cancers related to different organs including lymph (SRR = 19.44, 95% CI = 15.00-25.19), blood (SRR = 17.24, 95% CI = 12.92-23.01), nasopharynx (SRR = 3.97, 95% CI = 3.75-4.21), gallbladder (SRR = 3.46, 95% CI = 3.09-3.87), pancreas (SRR = 3.41, 95% CI = 3.07-3.79), respiratory system (SRR = 3.41, 95% CI = 3.27-3.57) and liver (SRR = 3.31, 95% CI = 3.09-3.56). Taken together, the present study provides evidence that general community population exposed to high level of PCP exhibits a broader spectrum of increased cancer risks as compared to occupational groups.[Cui Y, Liang L, Zhong Q, He Q, et al. 2017. Environ Pollut. 224:729-738.]

Organochlorine pesticides in carcinoma of the gallbladder: a case-control study.Carcinoma of the gallbladder is the third most common malignancy of the gastrointestinal tract in the Eastern Uttar Pradesh and Western Bihar regions of India. The main source of drinking water in this region is the river Ganges, which is heavily polluted with agricultural pesticides. Organochlorine pesticides were estimated in bile by gas liquid chromatography in 60 patients (30 carcinoma of the gallbladder and 30 cholelithiasis) to observe its association with aetiopathogenesis of carcinoma of the gallbladder. The mean biliary concentration of benzene hexachloride (BHC) was found to be significantly higher in carcinoma of the gallbladder (0.0471 ppm) than in cholelithiasis (0.0352 ppm) (P < 0.04). The mean biliary concentration of dichlorodiphenyltrichloroethane (DDT) was also significantly higher in carcinoma of the gallbladder (0.418 ppm) than in cholelithiasis (0.0103 ppm) (P < 0.03). Biliary aldrin and endosulfan concentrations were higher in carcinoma of the gallbladder (0.0008 and 0.00132 ppm) than in cholelithiasis (0.0005 and 0.0126 ppm) but the difference was statistically not significant (P < 0.06 and P < 0.9). The levels of pesticides in blood did not show significant differences in either carcinoma of the gallbladder or cholelithiasis. Significantly high biliary BHC and DDT concentrations suggest that these pesticides might be associated with gallbladder carcinogenesi.[Shukla VK, Rastogi AN, Adukia TK, et al. 2001. Eur J Cancer Prev. 10(2):153-6.]

Kidney/Renal Cancer

Occupational exposures and genetic susceptibility to urinary tract cancers: a systematic review and meta-analysis.This study aims to summarize the current knowledge on the relationship between genetic polymorphisms, occupational exposures, and urinary tract cancers. Authors searched MEDLINE, ISI Web of science, and SCOPUS online databases for all articles published in English language up to September 2016. A meta-analysis was performed to provide summary estimates for the association between a certain genetic polymorphism, occupational exposure and bladder cancer (BC) or kidney cancer (KC), when appropriate. Fifteen studies on BC and six on KC were deemed eligible for the review. With regard to BC, an overall odds ratio (OR) of 2.07 [95% confidence interval (CI): 1.38-3.09] for those with GSTM1 and an OR of 2.07 (95% CI: 1.38-3.09) for those with GSTT1 null genotype were reported when exposed to polycyclic aromatic hydrocarbons (PAHs). NAT2 slow genotype carriers had an OR of 3.59 (95% CI: 2.62-4.93) for BC when exposed to aromatic amines and an OR of 2.07 (95% CI: 1.36-3.15) when exposed to PAHs. With regard to KC and pesticide exposure, the meta-analysis reported an OR of 4.38 (95% CI: 2.28-8.41) for GSTM1 present genotype, an OR of 2.59 (95% CI: 1.62-4.15) for GSTT1-present genotype and an OR of 6.51 (95% CI: 2.85-14.89) for combined effects of GSTM1 and GSTT1 active genotypes. This meta-analysis indicates a possible association between the variant genotypes of GSTM1, GSTT1, NAT2 and SULT1A1, occupational exposure to aromatic amines or PAHs, and development of BC. Our results suggest that polymorphisms in GSTM1 and GSTT1 genes could influence the risk for developing KC in individuals occupationally exposed to pesticides.[Stojanovic J, Milovanovic S, Pastorino R, et al. 2017. Eur J Cancer Prev. doi: 10.1097/CEJ.0000000000000364]

Renal cell carcinoma, occupational pesticide exposure and modification by glutathione S-transferase polymorphisms.This study investigated associations between occupational pesticide exposure and renal cell carcinoma (RCC) risk. Study also considered whether this association could be modified by glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) genotypes. About 1097 RCC cases and 1476 controls from Central and Eastern Europe were interviewed to collect data on lifetime occupational histories. Occupational information for jobs held for at least 12 months duration was coded for pesticide exposures and assessed for frequency and intensity of exposure. GSTM1 and GSTT1 gene deletions were analyzed using TaqMan assays. A significant increase in RCC risk was observed among subjects ever exposed to pesticides. After stratification by genotypes, increased risk was observed among exposed subjects with at least one GSTM1 active allele but not among exposed subjects with two GSTM1 inactive alleles compared with unexposed subjects with two inactive alleles. Risk was highest among exposed subjects with both GSTM1 and GSTT1 active genotypes compared with unexposed subjects with at least one GSTM1 or T1 inactive genotype. In the largest RCC case-control study with genotype information conducted to date, it was observed that risk associated with pesticide exposure was exclusive to individuals with active GSTM1/T1 genotypes. These findings further support the hypothesis that glutathione S-transferase polymorphisms can modify RCC risk associated with occupational pesticide exposure.[Karami S, Boffetta P, Rothman N, Hung RJ, Stewart T, et al. 2008. Carcinogenesis. 29(8):1567-71]

Risk of childhood cancers associated with residence in agriculturally intense areas in the United StatesAn ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with moderate to high agriculture activity finds statistically significantly elevated risk for renal carcinoma at moderate agriculture activity (OR 2.3) and at high agriculture activity (OR 3.3). In regards to specific crops grown, the study finds a link between cotton crops and renal carcinomas (OR 6.9).[Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]

Glutathione S-transferases M1-1 and T1-1 as risk modifiers for renal cell cancer associated with occupational exposure to chemicals.Study aimed to investigate the possible interaction between occupational risk factors and genotype for glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) in renal cell cancer (RCC).One hundred patients with RCC and 200 outpatient controls were enrolled at Parma University Hospital. The polymorphisms of glutathione S-transferase M1-1 (GSTM1) and T1-1 (GSTT1) were investigated by PCR; occupational history was collected by a structured questionnaire. Subjects with GSTM1 present genotype showed higher risks for RCC, compared to GSTM1 null subjects, if exposed to metals or pesticides. The GSTT1 present genotype also enhanced the risk (about twofold) of RCC among subjects exposed to solvents and pesticides, compared with those GSTT1 null.Results support the hypothesis that GSTM1 and GSTT1 polymorphisms can interact with several occupational exposures to significantly modify the risk of RCC among exposed subjects.[Buzio L, De Palma G, Mozzoni P, et al. 2003. Occup Environ Med. 60(10):789-93]

Occupational risk factors for renal-cell carcinoma in DenmarkRisk of renal-cell carcinoma was found to be associated with employment as a truck driver, exposure to gasoline, other hydrocarbons, and insecticides and herbicides. The risk of renal-cell carcinoma was higher in the lower socioeconomic strata for both the men and the women.[Mellemgaard, A., et al. 1994. Scand J Work Environ Health 20(3):160-165.]

Cancer among farmers in central ItalyA case-referent study of Italian farmers finds a significantly increased risk of kidney cancer among farmers with greater than 10 years experience and a possible relationship between olives and potato growing and kidney cancer.[Forastiere, F, et al. 1993. Scand J Work Environ Health 19(6):382-389.]

Occupational risk factors for cancer of the larynx in Spain.Spain is one of the countries with the highest incidence of laryngeal cancer and, together with France, is the country with the lowest percentage of women with this disease. In order to identify the occupational risk factors associated with laryngeal cancer in this country a case-control study was performed. Cases included 85 patients with epidermoid carcinoma of the larynx diagnosed in "La Paz" Hospital, Madrid, between 1985 and 1987. A sample of 170 patients from the same hospital was used as control. The results of the study revealed that 56.5% of larynx cancer patients had a sedentary occupation working in the service sector. Exposure to insecticides or silica were strongest risk factors for laryngeal cancer.[Bravo MP, Espinosa J, Calero JR. 1990. Neoplasma. 37(4):477-81.]

Leukemia

Childhood Leukemia

A task-based assessment of parental occupational exposure to pesticides and childhood acute lymphoblastic leukemia.Associations between parental occupational pesticide exposure and childhood acute lymphoblastic leukemia (ALL) vary across studies, likely due to different exposure assessment methodologies. This study assessed parental occupational pesticide exposure from the year before pregnancy to the child's third year of life for 669 children diagnosed with ALL and 1021 controls. Authors conducted expert rating using task-based job modules (JM) to estimate exposure to pesticides among farmer workers, gardeners, agricultural packers, and pesticide applicators. Compared to complete JMs, partial JMs and JEM led to 3.1% and 9.4% of parents with pesticide exposure misclassified, respectively. Misclassification was similar in cases and controls. Using complete JMs, we observed an increased risk of ALL for paternal occupational exposure to any pesticides (OR=1.7; 95% CI=1.2, 2.5), with higher risks reported for pesticides to treat nut crops (OR=4.5; 95% CI=0.9, 23.0), and for children diagnosed before five years of age (OR=2.3; 95% CI: 1.3, 4.1). Exposure misclassification from JEM attenuated these associations by about 57%. Maternal occupational pesticide exposure before and after birth was not associated with ALL. The risk of ALL was elevated in young children with paternal occupational pesticide exposure during the perinatal period, using more detailed occupational information for exposure classification.[Gunier RB, Kang A, Hammond SK, Reinier K, et al. 2017. Environ Res. 156:57-62.]

Chemical exposure and infant leukaemia: development of an adverse outcome pathway (AOP) for aetiology and risk assessment research.Infant leukaemia (less 1 year old) is a rare disease of an in utero origin at an early phase of foetal development. Rearrangements of the mixed-lineage leukaemia (MLL) gene producing abnormal fusion proteins are the most frequent genetic/molecular findings in infant B cell-acute lymphoblastic leukaemia. In small epidemiological studies, mother/foetus exposures to some chemicals including pesticides have been associated with infant leukaemia; however, the strength of evidence and power of these studies are weak at best. Experimental in vitro or in vivo models do not sufficiently recapitulate the human disease and regulatory toxicology studies are unlikely to capture this kind of hazard. Here, we develop an adverse outcome pathway (AOP) based substantially on an analogous disease-secondary acute leukaemia caused by the topoisomerase II (topo II) poison etoposide-and on cellular and animal models. The hallmark of the AOP is the formation of MLL gene rearrangements via topo II poisoning, leading to fusion genes and ultimately acute leukaemia by global (epi)genetic dysregulation. The AOP condenses molecular, pathological, regulatory and clinical knowledge in a pragmatic, transparent and weight of evidence-based framework. This facilitates the interpretation and integration of epidemiological studies in the process of risk assessment by defining the biologically plausible causative mechanism(s). The AOP identified important gaps in the knowledge relevant to aetiology and risk assessment, including the specific embryonic target cell during the short and spatially restricted period of susceptibility, and the role of (epi)genetic features modifying the initiation and progression of the disease. Furthermore, the suggested AOP informs on a potential Integrated Approach to Testing and Assessment to address the risk caused by environmental chemicals in the future.[Pelkonen O, Terron A, Hernandez AF, et al. 2017. Arch Toxicol. 91(8):2763-2780.]

Spatial clustering of childhood leukaemia with the integration of the Paediatric Environmental History.Leukaemia remains the most common type of paediatric cancer and its aetiology remains unknown, but considered to be multifactorial. It is suggested that the initiation in utero by relevant exposures and/or inherited genetic variants and, other promotional postnatal exposures are probably required to develop leukaemia. This study aimed to map the incidence and analyse possible clusters in the geographical distribution of childhood acute leukaemia during the critical periods and to evaluate the factors that may be involved in the aetiology by conducting community and individual risk assessments. Researchers analysed all incident cases of acute childhood leukaemia diagnosed in a Spanish region during the period 1998-2013. At diagnosis, the addresses during pregnancy, early childhood and diagnosis were collected and codified to analyse the spatial distribution of acute leukaemia. A total of 158 cases of acute leukaemia were analysed. The crude rate for the period was 42.7 cases per million children. Among subtypes, acute lymphoblastic leukaemia had the highest incidence (31.9 per million children). A spatial cluster of acute lymphoblastic leukaemia was detected using the pregnancy address (p<0.05). The most common environmental risk factors related with the aetiology of acute lymphoblastic leukaemia, identified by the Paediatric Environmental History were: prenatal exposure to tobacco (75%) and alcohol (50%); residential and community exposure to pesticides (62.5%); prenatal or neonatal ionizing radiation (42.8%); and parental workplace exposure (37.5%). Study suggests that environmental exposures in utero may be important in the development of childhood leukaemia. Due to the presence of high-incidence clusters using pregnancy address, it is necessary to introduce this address into the childhood cancer registers. The Paediatric Environmental History which includes pregnancy address and a careful and comprehensive evaluation of the environmental exposures will allow us to build the knowledge of the causes of childhood leukaemia.[Cárceles-Álvarez A, Ortega-García JA, López-Hernández FA, et al. 2017. Environ Res. 156:605-612]

A review of risk factors for childhood leukemia.Leukemia is the most common cancer of childhood, with AML, CML, ALL and CLL being the most common. Environmental and genetic factors have been studied extensively in children with childhood leukemia. Other factors, such as the prenatal parental use of controlled substances, have not been investigated to the same degree. We review what is currently known about environmental and parental factors and the occurrence of leukemia in children.Electronic databases were searched for studies correlated pediatric leukemia with (1) ionizing radiation; (2) benzene; (3) parental drug use (4) parental alcohol use; (5) genetic factors.The two known significant environment risk factors for the occurrence leukemia are ionizing radiation and benzene. However, at least 4 studies have been published over the last century have looked at other environmental factors such as pesticides and drug and alcohol use as well as genetic factors such as gene fusions and translocations. We determined the risk of environmental and genetic factors that could be the cause of childhood leukemia in an effort to reduce the incidence of this disease.[Jin MW, Xu SM, An Q, Wang P. 2016. Eur Rev Med Pharmacol Sci. 20(18):3760-3764.]

Childhood Leukemia and Primary Prevention.Leukemia is the most common pediatric cancer, affecting 3800 children per year in the United States. Its annual incidence has increased over the last decades, especially among Latinos. Although most children diagnosed with leukemia are now cured, many suffer long-term complications, and primary prevention efforts are urgently needed. The early onset of leukemia-usually before 5 years of age-and the presence at birth of "pre-leukemic" genetic signatures indicate that pre- and postnatal events are critical to the development of the disease. In contrast to most pediatric cancers, there is a growing body of literature-in the United States and internationally-that has implicated several environmental, infectious, and dietary risk factors in the etiology of childhood leukemia, mainly for acute lymphoblastic leukemia, the most common subtype. For example, exposures to pesticides, tobacco smoke, solvents, and traffic emissions have consistently demonstrated positive associations with the risk of developing childhood leukemia. In contrast, intake of vitamins and folate supplementation during the preconception period or pregnancy, breastfeeding, and exposure to routine childhood infections have been shown to reduce the risk of childhood leukemia. Some children may be especially vulnerable to these risk factors, as demonstrated by a disproportionate burden of childhood leukemia in the Latino population of California. The evidence supporting the associations between childhood leukemia and its risk factors-including pooled analyses from around the world and systematic reviews-is strong; however, the dissemination of this knowledge to clinicians has been limited. To protect children's health, it is prudent to initiate programs designed to alter exposure to well-established leukemia risk factors rather than to suspend judgment until no uncertainty remains. Primary prevention programs for childhood leukemia would also result in the significant co-benefits of reductions in other adverse health outcomes that are common in children, such as detriments to neurocognitive development.[Whitehead TP, Metayer C, Wiemels JL, et al. 2016. Curr Probl Pediatr Adolesc Health Care. 46(10):317-352.]

Childhood Leukemia: A Preventable Disease.In contrast to most pediatric cancers, there is a growing body of literature, nationally and internationally, that has implicated the role of several environmental indoor and outdoor hazards in the etiology of childhood leukemia. For example, exposures to solvents, traffic, pesticides, and tobacco smoke have consistently demonstrated positive associations with the risk of developing childhood leukemia. Intake of vitamins and folate supplementation during the preconception period or pregnancy has been demonstrated to have a protective effect. Despite the strength of these findings, the dissemination of this knowledge to clinicians has been limited. Some children may be more vulnerable than others as documented by the high and increasing incidence of childhood leukemia in Hispanics. To protect children's health, it is prudent to establish programs to alter exposure to those factors with well-established associations with leukemia risk rather than to suspend judgment until no uncertainty remains. This is particularly true because other serious health outcomes (both negative and positive) have been associated with the same exposures. Study draws from historical examples to put in perspective the arguments of association versus causation, as well as to discuss benefits versus risks of immediate and long-term preventive actions.[Metayer C, Dahl G, Wiemels J, Miller M. 2016. Pediatrics. 138(Suppl 1):S45-S55.]

Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms.Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation of hematopoietic stem and/or progenitor cells (HSPCs) and drives uncontrolled proliferation and survival of the differentiation-blocked clone. Pediatric leukemia is phenotypically and genetically heterogeneous with an obscure etiology. The interaction between genetic factors and environmental agents represents a potential etiological driver. Although information is limited, the principal toxic mechanisms of potential leukemogenic agents (e.g., etoposide, benzene metabolites, bioflavonoids and some pesticides) include topoisomerase II inhibition and/or excessive generation of free radicals, which may induce DNA single- and double-strand breaks (DNA-DSBs) in early HSPCs. Chromosomal rearrangements (duplications, deletions and translocations) may occur if these lesions are not properly repaired. The initiating hit usually occurs in utero and commonly leads to the expression of oncogenic fusion proteins. Subsequent cooperating hits define the disease latency and occur after birth and may be of a genetic, epigenetic or immune nature (i.e., delayed infection-mediated immune deregulation). Here, we review the available experimental and epidemiological evidence linking pesticide exposure to infant and childhood leukemia and provide a mechanistic basis to support the association, focusing on early initiating molecular events.[Hernández AF, Menéndez P. 2016. Int J Mol Sci. 17(4):461.]

Passive exposure to agricultural pesticides and risk of childhood leukemia in an Italian community.Exposure to pesticides has been suggested as a risk factor for childhood leukemia, but definitive evidence on this relation and the specific pesticides involved is still not clear.We carried out a population-based case-control study in a Northern Italy community to assess the possible relation between passive exposure to agricultural pesticides and risk of acute childhood leukemia.We assessed passive pesticide exposure of 111 childhood leukemia cases and 444 matched controls by determining density and type of agricultural land use within a 100-m radius buffer around children's homes. We focused on four common crop types, arable, orchard, vineyard and vegetable, characterized by the use of specific pesticides that are potentially involved in childhood induced leukemia. The use of these pesticides was validated within the present study. We computed the odds ratios (OR) of the disease and their 95% confidence intervals (CI) according to type and density of crops around the children's homes, also taking into account traffic pollution and high-voltage power line magnetic field exposure. Childhood leukemia risk did not increase in relation with any of the crop types with the exception of arable crops, characterized by the use of 2.4-D, MCPA, glyphosate, dicamba, triazine and cypermethrin. The very few children (n=11) residing close to arable crops had an OR for childhood leukemia of 2.04 (95% CI 0.50-8.35), and such excess risk was further enhanced among children aged[Malagoli C, Costanzini S, Heck JE, Malavolti M, et al. 2016. Int J Hyg Environ Health. 219(8):742-748.]

Agricultural crop density and risk of childhood cancer in the midwestern United States: an ecologic study.This study examined the association of county level agricultural land use and the incidence of specific childhood cancers.Authors linked county-level agricultural census data (2002 and 2007) and cancer incidence data for children ages 0-4 diagnosed between 2004 and 2008 from cancer registries in six Midwestern states. Crop density (percent of county area that was harvested) was estimated for total agricultural land, barley, dry beans, corn, hay, oats, sorghum, soybeans, sugar beets, and wheat. Results found statistically significant exposure-response relationships for dry beans and total leukemias and acute lymphoid leukemias (ALL); oats and acute myeloid leukemias (AML); and sugar beets and total leukemias and ALL. State-level analyses revealed some additional positive associations for total leukemia and CNS tumors and differences among states for several crop density-cancer associations. However, some of these analyses were limited by low crop prevalence and low cancer incidence.The associations observed in this study need to be confirmed by analytic epidemiologic studies using individual level exposure data and accounting for potential confounders that could not be taken into account in this ecologic study.[Booth BJ, Ward MH, Turyk ME, Stayner LT. 2015. Environ Health. 14(1):82]

Home pesticide exposures and risk of childhood leukemia: Findings from the childhood leukemia international consortium.Some previous studies have suggested that home pesticide exposure before birth and during a child's early years may increase the risk of childhood leukemia. To further investigate this, authors pooled individual level data from 12 case-control studies in the Childhood Leukemia International Consortium. Exposure data were harmonized into compatible formats. The odds ratio (ORs) for acute lymphoblastic leukemia (ALL) associated with any pesticide exposure shortly before conception, during pregnancy and after birth were 1.39, 1.43 and 1.36, respectively. Corresponding ORs for risk of acute myeloid leukemia (AML) were 1.49, 1.55 and 1.08, respectively. There was little difference by type of pesticide used. The relative similarity in ORs between leukemia types, time periods and pesticide types may be explained by similar exposure patterns and effects across the time periods in ALL and AML, participants' exposure to multiple pesticides, or recall bias.[Bailey HD, Infante-Rivard C, Metayer C, Clavel J, Lightfoot T, et al. 2015. Int J Cancer. 137(11):2644-63.]

Household pesticide exposure and the risk of childhood acute leukemia in Shanghai, China.Childhood acute leukemia (AL) is the most common malignant tumor in children, but its etiology remains largely unknown. Study investigated the relationship between household exposure to pesticides and childhood AL. Between 2009 and 2010 in Shanghai, a total of 248 newly diagnosed cases of AL and 111 gender-, age-, and hospital-matched controls were included. Five nonspecific dialkyl phosphate (DAP) metabolites of organophosphate pesticides (OPPs) [including dimethyl phosphate (DMP), diethyl phosphate (DEP), dimethyl thiophosphate (DMTP), diethyl thiophosphate (DETP), and diethyl dithiophosphate (DEDTP)] in the urine were analyzed by gas chromatography. The results showed that the median DMP, DEP, DMTP, DETP, and DEDEP levels adjusted for creatinine (Cr) in cases were all significantly elevated compared with those in controls. The household use of mosquito repellent was significantly associated with an increased risk of childhood AL. Moreover, higher exposures were significantly associated with an elevated risk of childhood AL for DMs, DEs, and DAPs. Findings support the notion that the household use of pesticides may play a role in the etiology of childhood AL and provide some evidence to warrant further investigation of the link between household pesticide exposures and childhood AL in Shanghai.[Zhang Y, Gao Y, Shi R, Chen D, Wang X, et al. 2015. Environ Sci Pollut Res Int. 22(15):11755-63.]

Relationship between exposure to pesticides and occurrence of acute leukemia in Iran.One of the causes of acute leukemia can be exposure to certain chemicals such as pesticides. This study determined the relationship between exposure to pesticides and the occurrence of acute leukemia in Fars province, south of Iran. Between April 2011 and April 2013 in a case-control study conducted in Nemazee Hospital in Shiraz, Southern Iran; 314 subjects diagnosed with acute leukemia (94 pediatric cases and 220 adults) were enrolled to determine any correlation between exposure to pesticides and the occurrence.There was a history of exposure to pesticides among 85% of pediatric cases an d 69% of their controls and 83% of adult cases and 75% of their controls while 87.5% of pediatric cases and 90% of adult cases reported exposure to intermediate and high doses of pesticides and among the controls, the exposure to low doses of pesticides was 70.5% and 65%, respectively. Exposure to indoor pesticides was seen among most of cases and controls. Being a farmer was at a significantly more increased risk of developing acute leukemia in comparison to other jobs, especially for their children. Exposure to pesticides was shown to be one of the most important causes of acute leukemia.[Maryam Z, Sajad A, Maral N, Zahra L, et al. 2015. Asian Pac J Cancer Prev. 16(1):239-44.]

Residential Exposure to Pesticide During Childhood and Childhood Cancers: A Meta-Analysis.In this meta-analysis, authors aimed to examine associations between residential childhood pesticide exposures and childhood cancers.The literature search yielded 277 studies that met inclusion criteria.Sixteen studies were included in the meta-analysis, and authors found that childhood exposure to indoor but not outdoor residential insecticides was associated with a significant increase in risk of childhood leukemia (odds ratio [OR] = 1.47; 95% CI, 1.26-1.72; I(2) = 30%) and childhood lymphomas (OR = 1.43; 95% CI, 1.15-1.78; I(2) = 0%). A significant increase in risk of leukemia was also associated with herbicide exposure (OR = 1.26; 95% CI, 1.10-1.44; I(2) = 0%). Results from this meta-analysis indicated that children exposed to indoor insecticides would have a higher risk of childhood hematopoietic cancers. Additional research is needed to confirm the association between residential indoor pesticide exposures and childhood cancers. Meanwhile, preventive measures should be considered to reduce children's exposure to pesticides at home.[Chen M, Chang CH, Tao L, Lu C. 2015. Pediatrics. 136(4):719-29.]

Maternal factors and risk of childhood leukemia.The aim of this study was to examine association of childhood leukemia with maternal factors especially during pregnancy, to help in avoiding risk factors.This case-control study included children younger than 18 years diagnosed with leukemia from 2008 to 2012. Statistically significant associations between risk of childhood leukemia with mother's education , occupation and pesticides exposure during pregnancy were found. However, there were no significant links with maternal age, history of fetal loss, history of radiography during pregnancy, history of drug intake and infection during pregnancy.The results showed increased risk of leukemia in children whose mothers were working in agriculture and were exposed to pesticides during pregnancy. The further study needs to be investigated to know association of various maternal risk factors with leukemia which remained unknown in this study.[Kumar A, Vashist M, Rathee R. 2014. Asian Pac J Cancer Prev. 15(2):781-4.]

Parental occupational pesticide exposure and the risk of childhood leukemia in the offspring: findings from the childhood leukemia international consortium.Maternal occupational pesticide exposure during pregnancy and/or paternal occupational pesticide exposure around conception have been suggested to increase risk of leukemia in the offspring. Authors pooled individual level data from 13 case-control studies participating in the Childhood Leukemia International Consortium (CLIC). Using exposure data from mothers of 8,236 cases, and 14,850 controls, and from fathers of 8,169 cases and 14,201 controls the odds ratio (OR) for maternal exposure during pregnancy and the risk of acute lymphoblastic leukemia (ALL) was 1.01 and for paternal exposure around conception 1.20. For acute myeloid leukemia (AML), the OR for maternal exposure during pregnancy was 1.94 and for paternal exposure around conception 0.91. Finding of a significantly increased risk of AML in the offspring with maternal exposure to pesticides during pregnancy is consistent with previous reports. Study also found a slight increase in risk of ALL with paternal exposure around conception which appeared to be more evident in children diagnosed at the age of 5 years or more and those with T cell ALL which raises interesting questions on possible mechanisms.[Bailey HD, Fritschi L, Infante-Rivard C, Glass DC, et al. 2014. Int J Cancer. 135(9):2157-72.]

Exposure to herbicides in house dust and risk of childhood acute lymphoblastic leukemia.Study examines the association between exposure to herbicides and childhood acute lymphoblastic leukemia (ALL). Dust samples were collected from homes of 269 ALL cases and 333 healthy controls (<8 years of age at diagnosis/reference date and residing in same home since diagnosis/reference date) in California, using a high-volume surface sampler or household vacuum bags. Amounts of agricultural or professional herbicides (alachlor, metolachlor, bromoxynil, bromoxynil octanoate, pebulate, butylate, prometryn, simazine, ethalfluralin, and pendimethalin) and residential herbicides (cyanazine, trifluralin, 2-methyl-4-chlorophenoxyacetic acid (MCPA), mecoprop, 2,4-dichlorophenoxyacetic acid (2,4-D), chlorthal, and dicamba) were measured. The risk of childhood ALL was associated with dust levels of chlorthal; compared to homes with no detections, ORs for the first, second, and third tertiles were 1.49, 1.49, and 1.57, respectively. The magnitude of this association appeared to be higher in the presence of alachlor. No other herbicides were identified as risk factors of childhood ALL. The data suggest that home dust levels of chlorthal, and possibly alachlor, are associated with increased risks of childhood ALL.[Metayer C, Colt JS, Buffler PA, Reed HD, et al. 2013. J Expo Sci Environ Epidemiol. 23(4):363-70.]

Pyrethroid pesticide exposure and risk of childhood acute lymphocytic leukemia in Shanghai.Significant amounts of pyrethroid pesticides are used throughout China. Previous studies have suggested that exposure to pesticides may increase the risk of childhood cancer; however, few studies have focused on pyrethroid metabolites. This study investigated five nonspecific metabolites of pyrethroid pesticides found in children's urine and examined the correlation with childhood leukemia. A hospital-based case-control study of childhood acute lymphocytic leukemia (ALL) in Shanghai between 2010 and 2011 was carried out and included 176 children aged 0-14 years and 180 controls matched for age and sex. Compared with those in the lowest quartiles of total and individual metabolites, the highest quartiles were associated with an approximate 2-fold increased risk of ALL [total metabolites: odds ratio (OR) = 2.75, 1.43-5.29; cis-DCCA: OR = 2.21; trans-DCCA: OR = 2.33; and 3-PBA: OR = 1.84], and most of the positive trends were significant. Findings suggest that urinary levels of pyrethroid metabolites may be associated with an elevated risk of childhood ALL and represent a previously unreported quantitative exposure assessment for childhood leukemia.[Ding G, Shi R, Gao Y, Zhang Y, Kamijima M, et al. 2012. Environ Sci Technol. 46(24):13480-7]

Risk of childhood acute lymphoblastic leukaemia following parental occupational exposure to pesticidesStudy was performed to ascertain whether there was an association between parental occupational exposure to pesticides and increased risk of acute lymphoblastic leukaemia (ALL) in the offspring. A population-based case-control study of childhood ALL was conducted in Australia. Information about the occupational pesticide exposure of mothers and fathers was collected using job-specific modules. Information on the types and extent of pesticide exposure was collected for mothers and fathers before and around the time of conception, and also for mothers during pregnancy for the index case or control and for 1 year after birth. Paternal occupational exposure to pesticides before or around conception was not related to increased risk of childhood ALL. There was a low prevalence of occupational exposure to pesticides among women that reduced after birth. Paternal occupational exposure to pesticides was not found to be associated with an increased risk of acute lymphoblastic leukaemia in the offspring. The study was underpowered with respect to maternal exposure to pesticides.[Glass DC, Reid A, Bailey HD, et al. 2012. Occup Environ Med. 69(11):846-9.]

Exposure to pesticides and risk of childhood cancer: a meta-analysis of recent epidemiological studies.The authors performed a meta-analysis of case-control and cohort studies to clarify the possible relationship between exposure to pesticides and childhood cancers.Two cohort and 38 case-control studies were selected for the first meta-analysis.Meta-analysis of the three cohort studies did not show any positive links between parental pesticide exposure and childhood cancer incidence. However, the meta-analysis of the 40 studies with OR values showed that the risk of lymphoma and leukaemia increased significantly in exposed children when their mother was exposed during the prenatal period (OR=1.53; 95% CI 1.22 to 1.91 and OR=1.48; 95% CI 1.26 to 1.75). The risk of brain cancer was correlated with paternal exposure either before or after birth (OR=1.49; 95% CI 1.23 to 1.79 and OR=1.66; 95% CI 1.11 to 2.49). The OR of leukaemia and lymphoma was higher when the mother was exposed to pesticides.Despite some limitations in this study, the incidence of childhood cancer does appear to be associated with parental exposure during the prenatal period.[Vinson F, Merhi M, Baldi I, Raynal H, Gamet-Payrastre L. 2011. Occup Environ Med. 68(9):694-702.]

Exposure to professional pest control treatments and the risk of childhood acute lymphoblastic leukemia.Previous studies suggest that exposure to pesticides increases the risk of childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to investigate whether professional pest treatments in or around the home before birth or during childhood increased the risk of childhood ALL. Data from 388 cases and 870 frequency-matched controls were analyzed using unconditional logistic regression, adjusting for study matching variables and potential confounders, to calculate odds ratios (ORs).The ORs for any professional pest control treatments were 1.19 in the year before pregnancy, 1.30 during pregnancy and 1.24 for those done after the child's birth. The ORs for exposure after birth were highest when it occurred between the ages of two and three years. ORs were elevated for termite treatments before birth. ORs were higher for pre-B than T cell ALL and for t(12;21) (ETV6-Runx-1) than other cytogenetic sub-types. Results provide some evidence of a modestly increased risk of ALL for professional pest control treatments done during the index pregnancy and possibly in the child's early years.[Bailey HD, Armstrong BK, de Klerk NH, et al. 2011. Int J Cancer. 129(7):1678-88]

Residential exposures to pesticides and childhood leukemiaThe aim of this study was to conduct a systematic review of published studies on the association between residential/household/domestic exposure to pesticides and childhood leukaemia, and to provide a quantitative estimate of the risk. Publications in English were searched in MEDLINE (1966-31 December 2009) and from the reference list of identified publications. Separate analyses were conducted after stratification for exposure time windows, residential exposure location, biocide category and type of leukaemia. Statistically significant associations with childhood leukaemia were observed when combining all studies. Exposure during and after pregnancy was positively associated with childhood leukaemia, with the strongest risk for exposure during pregnancy. Other stratifications showed the greatest risk estimates for indoor exposure, for exposure to insecticides as well as for acute non-lymphocytic leukaemia (ANLL). Outdoor exposure and exposure of children to herbicides (after pregnancy) were not significantly associated with childhood leukaemia. Findings support the assumption that residential pesticide exposure may be a contributing risk factor for childhood leukaemia but available data were too scarce for causality ascertainment. It may be opportune to consider preventive actions, including educational measures, to decrease the use of pesticides for residential purposes and particularly the use of indoor insecticides during pregnancy.[Van Maele-Fabry G, Lantin AC, Hoet P, Lison D. 2011. Environ Int. 37(1):280-91.]

Residential pesticides and childhood leukemia: a systematic review and meta-analysis.Study is a systematic review and meta-analysis of previous observational epidemiologic studies examining the relationship between residential pesticide exposures during critical exposure time windows (preconception, pregnancy, and childhood) and childhood leukemia. Exposures during pregnancy to unspecified residential pesticides insecticides, and herbicides were positively associated with childhood leukemia. Exposures during childhood to unspecified residential pesticides and insecticides were also positively associated with childhood leukemia, but there was no association with herbicides. Positive associations were observed between childhood leukemia and residential pesticide exposures. Further work is needed to confirm previous findings based on self-report, to examine potential exposure-response relationships, and to assess specific pesticides and toxicologically related subgroups of pesticides in more detail.[Turner MC, Wigle DT, Krewski D. 2011. Cien Saude Colet. 16(3):1915-31.]

Pediatric acute lymphoblastic leukemia and exposure to pesticides.A case-control study of children diagnosed with ALL and their mothers in the Washington DC area finds an association between the development of childhood ALL and common household pesticides, as ALL child-mother pairs have elevated levels for the organophosphate metabolites diethylthiophosphate and diethyldithiophosphate and more case mothers (33%) than controls (14%) reported using insecticides in the home.[Soldin, O.P., et al. 2009. Therapeutic Drug Monitoring 31(4):495-501]

Residential proximity to agricultural pesticide applications and childhood acute lymphoblastic leukemiaA population based, case control study in California using residential histories and proximity to agricultural pesticide use shows an elevated risk of childhood ALL associated with moderate exposure, but not high exposure, to pesticides classified as organophosphates, chlorophenoxy herbicides, and triazines, and with agricultural pesticides used as insecticides or fumigants.[Rull, R.P., et al. 2009. Environ Res 109(7):891-9]

Parental occupational exposure to pesticides and the risk of childhood leukemia in Costa Rica.In a Costa Rica population-based, case-control study, researchers find parental occupational exposure to pesticides increases the risk of childhood leukemia. Maternal pesticide exposure doubles offspring leukemia risk, whether before conception (OR 2.4), or during the first (OR 22) or second trimesters (OR 4.5) the risk is significant. Paternal pesticide exposure during the second trimester also increases risk (1.5 OR) in offspring. In regards to organophosphates, maternal exposure during the first trimester is three and a half times higher (OR 3.5). Exposure to benzimidazole pesticides during pregnancy also has twice the risk for childhood leukemia (OR 2.2)[Monge, P., et al. 2007. Scandinavian Journal of Work, Environment and Health 33(4):293-303]

Household exposure to pesticides and risk of childhood acute leukaemiaA study of household pesticide exposure and childhood acute leukemia finds an increased risk for maternal home insecticide use during pregnancy and during childhood, and with garden insecticide use and fungicide use during childhood. Pyrethroid and lindane lice shampoo treatment is also associated with childhood acute leukemia. The majority of the childhood cancers were acute lymphocytic leukemia.[Menegaux, F., et al. 2006. Occup Environ Med 63(2):131-134]

Agricultural pesticide use and childhood cancer in California.Looking at residential proximity to agricultural pesticides, a population-based case-control study of early childhood cancer, ages 0-4 years, in California finds an elevated risk for leukemia associated with probable and possible carcinogen use and with nearby agricultural applications of organochlorines and organophosphates during pregnancy (metam sodium OR 2.05 and dicofol OR 1.83)[Reynolds, P, et al. 2005. Epidemiology 16(1):93-100]

Critical windows of exposure to household pesticides and risk of childhood leukemia.A case-control study in California finds a significant increased risk of childhood leukemia to the use of professional indoor pesticide applications at any time from one year before birth to three years after. In addition, frequency of exposure to pesticides was also linked with increased risk[Ma, X., et al. 2002. Critical windows of exposure to household pesticides and risk of childhood leukemia. Environmental Health Perspectives 110:955-960]

Home pesticide use and childhood cancer: A case-control studyA case-control study in Denver finds home use of pest strips containing dichlorvos is linked to childhood leukemia. The highest risk is found for exposure during the last 3 months of pregnancy, for exposure during the 2 years prior to diagnosis, and for exposure from birth through 2 years prior to diagnosis.[Leiss, J., et al. 1995. American Journal of Public Health 85:249-252]

Childhood leukemia and parents' occupational and home exposures.A case-control study in California finds household pesticide use can more than triple the risk of childhood leukemia and that garden pesticides increase the risk to over six-fold.[Lowengart, R., et al. 1987. Journal of the National Cancer Institute 79(1):39-46]

Adult Leukemia

The impact of Agent Orange exposure on presentation and prognosis of patients with chronic lymphocytic leukemia.Exposure to Agent Orange (AO) and the contaminating chemical 2,3,7,8-tetrachlorodibenzodioxin (TCDD) has been associated with the development of chronic lymphocytic leukemia (CLL). Of the 195 veterans diagnosed with CLL from 2001 to 2010 in a retrospective cohort from the Minneapolis Veterans Affairs Medical Center, 33 (17%) were exposed to AO. Prognostic factors including Rai stage, lymphocyte doubling time and cytogenetics did not differ between exposed and unexposed patients. Exposed patients were younger at diagnosis (61 vs. 72 years, p < 0.0001) and time to CLL treatment was shorter (9.6 vs. 30.2 months, p = 0.02). Overall survival did not differ between exposed and unexposed patients on Kaplan-Meier analysis, but when adjusted for age, AO exposure had a hazard ratio of death of 1.8 compared to non-exposure. The high estimate of the mortality hazard combined with the relatively low numbers in the exposure group suggests that further examination in a larger patient population is warranted.[Baumann Kreuziger LM, Tarchand G, Morrison VA. 2014. Leuk Lymphoma. 55(1):63-6.]

Epidemiology of leukemia and multiple myeloma in Golestan, Iran.The aim of this paper was to present the incidence rates of leukemia and multiple myeloma (MM) in Golestan province located in northeastern Iran during 2004-2009.This was a descriptive cross-sectional study. Data on newly diagnosed (incident) leukemia and MM cases were obtained from collected from Golestan population-based cancer registry. Totally, 11036 new cancer cases were registered in GPRC from 2004-2009. Leukemia and MM accounted for 693 and 124 of cases, respectively. The mean age in patients with leukemia and MM was 43.8 and 62.4 years, respectively. The ASRs for leukemia among men and women were 10.4 and 7.8, respectively. The ASRs for MM were 2.1 and 2 in men and women, respectively. The rate of leukemia was significantly higher in rural areas whereas the incidence of MM was higher in urban areas. High exposure to pesticides and other agricultural related products may be a possible explanation for epidemiological pattern of leukemia in this area. Determining and controlling important risk factors, especially environmental factors, of leukemia may lead to decrease in its burden in Golestan province of Iran.[Rajabli N, Naeimi-Tabeie M, Jahangirrad A, et al. 2013.Asian Pac J Cancer Prev. 14(4):2333-6.]

Occupational exposure to terbufos and the incidence of cancer in the Agricultural Health StudyStudy investigated associations between use of terbufos and the incidence of cancer. The Agricultural Health Study is a prospective cohort study of 57,310 licensed pesticide applicators from Iowa and North Carolina. Detailed information about 50 pesticides, including terbufos, and potential confounders was obtained from self-administered questionnaires. Overall cancer risk was slightly increased among terbufos users. Suggestive associations were observed between terbufos use and cancers of the prostate and lung, leukemia, and non-Hodgkin's lymphoma, although the exposure-response gradients were non-monotonic and p for trends were not significant. However, cautious interpretation of these results is warranted by the lack of existing experimental and epidemiologic evidence to support carcinogenic effects of terbufos.[Bonner, M.R., et al. 2010. Cancer Causes Control 21(6):871-7]

Pesticide sales and adult male cancer mortality in Brazil.A study of pesticides sales in different parts of Brazil and cancer mortality rates a decade later finds a statistically significant correlation between pesticide sales with the mortality rates for leukemia and cancer of the lip, esophagus, pancreas, and prostate.[Chrisman, J.D., et al. 2009. Int J Hyg Environ Health ;212(3):310-21]

Cancer mortality in the U.S. flour industryA study of workers employed in U.S. flour mills, where according to the study author’s, “pesticides are used more frequently than in other segments of the industry,” an increased risk for developing leukemia is found.[Alavanja, M.C., et al. 1990. J Natl Cancer Inst 82(10):840-848]

Pesticide sales and adult male cancer mortality in Brazil.A study of pesticides sales in different parts of Brazil and cancer mortality rates a decade later finds a statistically significant correlation between pesticide sales with the mortality rates for leukemia and cancer of the lip, esophagus, pancreas, and prostate.[Chrisman, J.D., et al. 2009. Int J Hyg Environ Health ;212(3):310-21]

Cancer incidence among farmers exposed to lindane while sheep dippingThe objective of this study was to determine whether site-specific cancer incidence among farmers exposed to the insecticide lindane (g-hexachlorocyclohexane) while dipping sheep differs from that of the general population in Iceland.Cohorts of 7882 men and 429 women, who, according to records on sheep dipping, were sheep owners, were followed from 1962 to 2003 in the Cancer Registry for cancer incidence.For men the standardized incidence ratio (SIR) for all cancer sites was 0.79, with a 95% confidence interval (95% CI) of 0.76-0.83. For both the men and the women a significantly increased risk for lip cancer was found, with SIR of 1.50 (95% CI 1.08-2.04) and 9.09 (95% CI 1.02-32.82), respectively. Cancer of the lip was the only cancer type in significant excess among both genders, and the stomach cancer rates were near unity, but, in previous studies on Icelandic farmers, an increase had been found for stomach cancer. The site-specific cancer incidence for sheep-dipping farmers did not differ substantially from that of the general population.[Rafnsson V. 2006. Scand J Work Environ Health. 32(3):185-9.]

Incidence of lip cancer in the male Norwegian agricultural populationStudy explored lip cancer (LC) associations with work environmental exposures in a record-linkage study of Norwegian farmers. A cohort of 131,243 male Norwegian farmers born 1925-1971 was established by cross-linkage of national registers and followed up through 1999 for incident LC, (ICD-7 site 140) in the Cancer Registry of Norway. Study identified 108 LC cases (rate 4.4 per 100,000 person-years) and found LC to be moderately associated with horses on the farm (RR = 1.6, CI = 1.0-2.4), construction work employment (RR = 1.7, CI = 1.1-2.6), pesticide use (RR = 0.7, CI = 0.4-1.0), grain production (RR = 1.3, CI = 0.9-2.1) and increasing levels of fungal forecasts (RR = 1.6, CI = 0.9-2.8 in the highest two quartiles).Moderate associations of LC with grain production and fungal forecasts and the negative association with pesticide could possibly be explained by exposure to immunosuppressive mycotoxins. Some of the associations observed could be explained by solar exposure.[Nordby KC, Andersen A, Kristensen P. 2004. Cancer Causes Control. 15(6):619-26.]

Liver/Hepatic Tumors

Non‑infective occupational risk factors for hepatocellular carcinoma: A review (Review)Liver cancer is the second leading worldwide cause of cancer‑associated mortalities. Hepatocellular carcinoma, which accounts for the majority of liver tumors, ranks fifth among types of human cancer. Well‑established risk factors for liver cancer include the hepatitis B and C viruses, aflatoxins, alcohol consumption, and oral contraceptives. Tobacco smoking, androgenic steroids, and diabetes mellitus are suspected risk factors. Current knowledge regarding non‑infective occupational risk factors for liver cancer is inconclusive. The relevance of liver disorders to occupational medicine lies in the fact that the majority of chemicals are metabolized in the liver, and toxic metabolites generated via metabolism are the predominant cause of liver damage. However, their non‑specific clinical manifestations that are similar in a number of liver diseases make diagnosis difficult. Furthermore, concomitant conditions, such as viral hepatitis and alcohol or drug abuse, may mask liver disorders that result from occupational hepatotoxic agents and block the demonstration of an occupational cause. The identification of environmental agents that result in human cancer is a long and often difficult process. The purpose of the present review is to summarize current knowledge regarding the association of non‑infective occupational risk exposure and HCC, to encourage further research and draw attention to this global occupational public health problem.[Ledda C, Loreto C, Zammit C, Marconi A, et al. 2017. Mol Med Rep. 15(2):511-533.]

The association of cancer risks with pentachlorophenol exposure: Focusing on community population in the areas along certain section of Yangtze River in China.Pentachlorophenol (PCP) was used in large quantities, and mainly for killing the intermediate host snails of schistosome in China, thereby resulting in ubiquitous PCP residue in the environment. However, studies considering the carcinogenicity of PCP for humans mainly focused on occupational workers, and the actual carcinogenicity of PCP for general population is uncertain. To investigate the association between cancer risks and PCP exposure in a community population, an ecological study was conducted in three contaminated areas along the Yangtze River. Standardized rate ratio (SRR) was calculated to represent the risk of cancer incidence, by using incidence in the low PCP exposure category as the reference group. A total of 15,962 cancer records were collected, and 76 water samples and 213 urine samples in three areas were examined. Findings suggested that compared with the low PCP group, the high PCP group had significantly excessive incidences of various cancers related to different organs including lymph (SRR = 19.44, 95% CI = 15.00-25.19), blood (SRR = 17.24, 95% CI = 12.92-23.01), nasopharynx (SRR = 3.97, 95% CI = 3.75-4.21), gallbladder (SRR = 3.46, 95% CI = 3.09-3.87), pancreas (SRR = 3.41, 95% CI = 3.07-3.79), respiratory system (SRR = 3.41, 95% CI = 3.27-3.57) and liver (SRR = 3.31, 95% CI = 3.09-3.56). Taken together, the present study provides evidence that general community population exposed to high level of PCP exhibits a broader spectrum of increased cancer risks as compared to occupational groups.[Cui Y, Liang L, Zhong Q, He Q, et al. 2017. Environ Pollut. 224:729-738.]

Myclobutanil worsens nonalcoholic fatty liver disease: An in vitro study of toxicity and apoptosis on HepG2 cells.Myclobutanil is a conazole class fungicide widely used as an agrichemical. Its widespread use has raised the issue of possible health risks for agrarian communities and the general population, which can be exposed to residues present in food and drinking water. The toxicities identified include adverse effects on liver and kidney and on the development of male reproductive organs. Since the liver is the first-line organ in the defense against xenobiotics, toxic effects on hepatic metabolism cause degeneration, necrosis, and tissue hypertrophy. Therefore, we investigated myclobutanil's effects on the human liver cell line HepG2. We found that myclobutanil increases the amount of fatty acids in these hepatic cells, as evaluated with Oil Red O staining, and progressively reduces cell viability from 1ppm to 500ppm. Analysis of biomarkers such as Bcl-xL/Bak and Mcl-1/Bak confirmed activation of cell death pathways at low doses. Therefore, myclobutanil may play an important role in the pathogenesis and progression of chronic hepatocellular diseases in humans.[Stellavato A, Lamberti M, Pirozzi AV, et al. 2016. Toxicol Lett. 262:100-104]

Mode of action analysis for pesticide-induced rodent liver tumours involving activation of the constitutive androstane receptor: relevance to human cancer risk.A number of non-genotoxic chemicals, including some pesticides, have been shown to increase the incidence of liver tumours in rats and/or mice. Frameworks for analysing the modes of action (MOAs) by which chemicals produce liver tumours in rodents and the relevance of such tumour data for human risk assessment have now been established. One common MOA for rodent liver tumour formation by non-genotoxic chemicals involves activation of the constitutive androstane receptor (CAR). Key and associative events for a CAR-activation MOA include receptor activation, liver hypertrophy, induction of cytochrome P450 enzyme activities, increased replicative DNA synthesis, altered hepatic foci and liver tumours. While some effects of rodent CAR activators can be observed in human liver, a major species difference is that, unlike rodents, CAR activators do not increase replicative DNA synthesis in human hepatocytes. The CAR-activation MOA for rodent liver tumour formation is thus not plausible for humans, and hence such compounds do not pose a hepatocarcinogenic hazard for humans.[Lake BG, Price RJ, Osimitz TG. 2015.Pest Manag Sci.71(6):829-34]

Pesticide exposure and hepatocellular carcinoma risk: A case-control study using a geographic information system (GIS) to link SEER-Medicare and California pesticide data.Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is associated with low survival. Study aimed to clarify the association between pesticide exposure and HCC by implementing a novel data linkage between Surveillance, Epidemiology, and End Results (SEER)-Medicare and California Pesticide Use Report (PUR) data using a geographic information system (GIS).Controls were frequency-matched to HCC cases diagnosed between 2000 and 2009 in California by year, age, race, sex, and duration of residence in California. ZIP Code exposure estimates were linked to subjects using Medicare-provided ZIP Codes to calculate pesticide exposure. Among California residents of agriculturally intensive areas, previous annual ZIP Code-level exposure to over 14.53kg/km2 of organochlorine pesticides (75th percentile among controls) was associated with an increased risk of HCC after adjusting for liver disease and diabetes (adjusted odds ratio [OR] 1.87). ZIP Code-level organochlorines were significantly associated with an increased risk of HCC among males (adjusted OR 2.76), but not associated with HCC among females (adjusted OR 0.83).This is the first epidemiologic study to use GIS-based exposure estimates to study pesticide exposure and HCC. Our results suggest that organochlorine pesticides are associated with an increase in HCC risk among males but not females.[VoPham T, Brooks MM, Yuan JM, Talbott EO, et al. 2015. Environ Res.143(Pt A):68-82.]

Evaluation of hepatotoxicity and clastogenicity of carbofuran in male Wistar rats.The present study examined the hepatotoxicity and clastogenic effects of carbofuran in rats. Male Wistar rats were exposed to carbofuran (p.o) at 0-5mg/kg bw for 5weeks. Carbofuran induced significant increase in the serum activity of gamma-glutamyltransferase when compared with the negative control, but not activity of serum alanine and aspartate aminotransferases. It also significantly induced micronucleated polychromatic erythrocytes formation in the bone marrow as compared with the control. The level of induction is dose dependent in both cases. In addition, there was significant higher number of hepatic cells in the cell/mm(2) assay for the group treated with carbofuran. Findings from this study suggest that carbofuran has clastogenic and hepatotoxic effects in rats. It therefore may constitute an environmental health risks in individuals so exposed.[Gbadegesin MA, Owumi SE, Akinseye V, Odunola OA. 2014. Food Chem Toxicol. 65:115-9.]

Impact of isomalathion on malathion cytotoxicity and genotoxicity in human HepaRG cells.In the present study, cytotoxicity and genotoxicity of malathion and isomalathion either individually or in combination, were assessed using the metabolically competent human liver HepaRG cell line. Isomalathion reduced cell viability starting at a 100 μM concentration after a 24h exposure. It also significantly induced caspase-3 activity in a dose-dependent manner starting at 5 μM. Co-exposure of both compounds resulted in decreased toxicity of isomalathion. By contrast, malathion and isomalathion either separately or in combination, slightly induced micronuclei formation at low concentrations and had additive genotoxic effects when combined at 25 μM. Individually or combined isomalathion directly inhibited activity of carboxyesterases which are involved in detoxication of malathion. Results showed that isomalathion was much more cytotoxic than malathion while both compounds had comparable genotoxic effects in HepaRG hepatocytes at low concentrations and brought further support to the importance of considering impurities and interactions during evaluation of health risks of pesticides.[Josse R, Sharanek A, Savary CC, Guillouzo A. 2014. Chem Biol Interact. 209:68-76]

Potential involvement of chemicals in liver cancer progression: an alternative toxicological approach combining biomarkers and innovative technologies.In order to evaluate the in vitro effects of chemicals present in the diet, study began by combining viability, real-time cellular impedance and high throughput screening data to identify a concentration "zone of interest" for the six xenobiotics selected: endosulfan, dioxin, carbaryl, carbendazim, p'p'DDE and hydroquinone. Study identified a single concentration of each pollutant allowing a modulation of the impedance in the absence of vital changes (nuclear integrity, mitochondrial membrane potential, cell death). Based on the number of observed modulations known to be involved in hepatic homeostasis dysfunction that may lead to cancer progression such as cell cycle and apoptosis regulators, EMT biomarkers and signal transduction pathways, authors then ranked the pollutants in terms of their toxicity. Endosulfan, was able to strongly modulate all the studied cellular processes in HepG2 cells, followed by dioxin, then carbendazim. Results of in vitro data indicate that these xenobiotics may contribute to the evolution and worsening of hepatocarcinoma.[Peyre L, Zucchini-Pascal N, de Sousa G, et al. 2014. Toxicol In Vitro. 28(8):1507-20.]

Global DNA methylation screening of liver in piperonyl butoxide-treated mice in a two-stage hepatocarcinogenesis model.To identify key molecules in piperonyl butoxide (PBO)-induced hepatocarcinogenesis, study searched hypermethylated genes using CpG island (CGI) microarrays in non-neoplastic liver cells as a source of proliferative lesions at 25 weeks after tumor promotion with PBO using mice. The study further performed methylation-specific polymerase chain reaction (PCR), real-time reverse transcription PCR, and immunohistochemical analysis in PBO-promoted liver tissues. Ebp4.1, Wdr6 and Cmtm6 increased methylation levels in the promoter region by PBO promotion, although Cmtm6 levels were statistically non-significant.Results suggest that PBO promotion may cause altered epigenetic gene regulation in non-neoplastic liver cells surrounding proliferative lesions to allow the facilitation of hepatocarcinogenesis. Both Wdr6 and Cmtm6 showed decreased expression in non-neoplastic liver cells in contrast to positive immunoreactivity in the majority of proliferative lesions produced by PBO promotion. These results suggest that both Wdr6 and Cmtm6 were spared from epigenetic gene modification in proliferative lesions by PBO promotion in contrast to the hypermethylation-mediated downregulation in surrounding liver cells. Considering the effective detection of proliferative lesions, these molecules could be used as detection markers of hepatocellular proliferative lesions and played an important role in hepatocarcinogenesis.[Yafune A, Kawai M, Itahashi M, et al. 2013. Toxicol Lett. 222(3):295-302]

Risk of hepatocellular carcinoma in workers exposed to chemicalsIn this study, a review of the literature found that while laboratory data clearly indicate that the liver is an important target of chemical carcinogenesis, epidemiological studies provide very limited evidence on occupational risk factors for HCC. Nevertheless, study found some case reports and epidemiological data showing a moderately increased risk of HCC development in people exposed to vinyl chloride, organic solvents, pesticides, polychlorinated biphenyls, and arsenic. Occupational exposure to chemicals may be another risk factor for HCC development, but the interpretation of currently available findings is limited by the small number of studies, questionable accuracy of the diagnosis of liver cancer, and potential confounding or modifying factors such as chronic hepatitis virus infection and alcohol consumption. Further relevant investigations are required for clarifying the actual contribution of occupational exposure to chemicals in HCC development.[Uccello M, Malaguarnera G, Corriere T, et al. 2012. Hepat Mon. 12(10 HCC):e5943.]

Risk of childhood cancers associated with residence in agriculturally intense areas in the United StatesAn ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with agricultural activity finds an elevated risk for hepatic tumors (OR 3.3) and for subtype hepatoblastoma (OR 4.0) at high agricultural activity (greater than 60% of county acreage devoted to farming).[Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]

Lung Cancer

Occupational Exposure to Pesticides and the Incidence of Lung Cancer in the Agricultural Health Study.Occupational pesticide use is associated with lung cancer in some, but not all, epidemiologic studies. In the Agricultural Health Study (AHS), we previously reported positive associations between several pesticides and lung cancer incidence.We evaluated use of 43 pesticides and 654 lung cancer cases after 10 years of additional follow-up in the AHS, a prospective cohort study comprising 57,310 pesticide applicators from Iowa and North Carolina.Information about lifetime pesticide use and other factors was ascertained at enrollment (1993-1997) and updated with a follow-up questionnaire (1999-2005). Hazard ratios were elevated in the highest exposure category of lifetime days of use for pendimethalin (1.50; 95% CI: 0.98, 2.31), dieldrin (1.93; 95% CI: 0.70, 5.30), and chlorimuron ethyl (1.74; 95% CI: 1.02, 2.96), although monotonic exposure-response gradients were not evident. The HRs for intensity-weighted lifetime days of use of these pesticides were similar. For parathion, the trend was statistically significant for intensity-weighted lifetime days (p = 0.049) and borderline for lifetime days (p = 0.073). None of the remaining pesticides evaluated was associated with lung cancer incidence.These analyses provide additional evidence for an association between pendimethalin, dieldrin, and parathion use and lung cancer risk. We found an association between chlorimuron ethyl, a herbicide introduced in 1986, and lung cancer that has not been previously reported. Continued follow-up is warranted.[Bonner MR1, Freeman LE, Hoppin JA, Koutros S, Sandler DP, et al. 2017. Environ Health Perspect. 125(4):544-551.]

Chronic exposure to chlorophenol related compounds in the pesticide production workplace and lung cancer: a meta-analysis.Chlorophenols (CPs) and related phenoxyacetic acids (PAs) are pesticide groups contaminated with highly toxic 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) during production. PAs and CPs exposure is associated with risk of cancer, but the situation regarding lung cancer has not been clearly defined. Study is a meta-analysis of published researches to evaluate relationship between chronic exposure to PAs and CPs in pesticide production workplaces and the risk of lung cancer.Five papers with six reports were included in the final analysis. The standardized mortality rate for lung cancer from the random model was 1.18 with moderate heterogeneity. Publication bias was not found for included studies in meta-analysis (p=0.9).Our findings has strengthen the evidence of lung cancer from chronic exposure to chlorophenol related compounds (PAs, CPs).[Zendehdel R, Tayefeh-Rahimian R, Kabir A. 2014. Asian Pac J Cancer Prev. 15(13):5149-53.]

Cancer Incidence Among Pesticide Applicators Exposed to Chlorpyrifos in the Agricultural Health StudyThe rate of lung cancer increases among those workers with higher levels of chlorpyrifos exposure. Individuals in the highest quartile of lifetime exposure-days had more than twice the risk of lung cancer compared with those with no chlorpyrifos exposure. Even when study authors controlled for other factors such as smoking, family history of cancer, and age, the chlorpyrifos link to lung cancer remained.[Lee WJ, et al. 2004. J Natl Cancer Inst. 96(23):1781-9.]

Lung cancer and other causes of death among licensed pesticide applicators.A cohort study of causes of death among licensed pesticide applicators in Florida finds excess deaths due to lung cancer. Although individuals’ tobacco use was not available, a 1983 study of causes of death among licensed pesticide applicators in Florida finds excess deaths due to cancer of the lungs and that the risk increased with the number of years licensed. Mortality is shown to be greatest for those first licensed before age 40 than among those individuals licensed after age 40.[Blair, A., et al. 1983. J Natl Cancer Inst 71(1):31-37]

Lymphoma

Hodgkin's Lymphoma

Exposures to multiple pesticides and the risk of Hodgkin lymphoma in Canadian men.Study's aim was to determine the risk of Hodgkin lymphoma (HL) associated with exposures to multiple pesticides grouped by various classes, including carcinogenic classifications. Data collected in the Cross-Canada Study of Pesticides and Health, a population-based incident case-control study in six provinces conducted between 1991 and 1994, were analyzed using unconditional logistic regression. Overall, there was an increase in the risk of HL among all subjects who reported use of five or more insecticides (OR 1.88) and among subjects younger than 40 who reported use of two acetylcholinesterase inhibitors (OR 3.16). There was an elevated odds ratio associated with reported use of three or more probably carcinogenic pesticides (OR 2.47), but no increase in risk for use of possibly carcinogenic pesticides. The risk of HL from reported use of fungicides or any pesticides was greater for cases diagnosed before age 40 than for cases diagnosed at or after age 40. This study found associations between HL and fungicides, insecticides, specifically acetylcholinesterase inhibitors, and pesticides previously identified as probable human carcinogens.[Navaranjan G, Hohenadel K, Blair A, Demers PA, et al. 2013. Cancer Causes Control. 24(9):1661-73]

Hodgkin lymphoma and pesticides exposure in men: a Canadian case-control study.The objective of this study was to investigate the putative associations of specific pesticides with Hodgkin lymphoma. A population-based, case-control study of Hodgkin lymphoma was conducted among males in six regions of Canada. Comparisons of 316 Hodgkin lymphoma cases and 1506 controls identified several factors as predictors for increased Hodgkin lymphoma risk: family history of cancer, exposure to the insecticide chlorpyrifos [OR (95% CI) = 1.19 (1.03, 1.37)], and previous diagnosis of acne or shingles. The increased risk of developing Hodgkin lymphoma detected among Canadian men who used chlorpyrifos must be interpreted cautiously; however the strength of its association indicates that it requires investigation in other populations.[Karunanayake CP, Spinelli JJ, McLaughlin JR, et al. 2012. J Agromedicine. 17(1):30-9.]

Ethnicity and incidence of Hodgkin lymphoma in Canadian populationResearch has shown that ethnicity is a significant predictor of Hodgkin lymphoma (HL). Other risk factors important in the etiology of HL are medical history and exposure to pesticides. In this report authors investigated the association between ethnicity and HL in the presence of medical history, and exposure to pesticides.In the study population, the distribution of ethnic groups was: 38.5% North American, 15% British, 8.4% Western European, 8.2% Eastern European, 1.7% Asian, 1.4% Scandinavian and 27% of other ethnic origin. Compared to North Americans (i) the risk of HL was greater among the Eastern European descendents (Odds Ratio (ORadj): 1.82) and Western European (ORadj: 1.62) descent population; and (ii) the risk of HL was lower in Asian descents. Exposure to individual herbicide dichlorprop showed an increased risk of HL (ORadj: 6.35).[Pahwa P, Karunanayake CP, Spinelli JJ, et al. 2009. BMC Cancer. 9:141]

Risk of childhood cancers associated with residence in agriculturally intense areas in the United StatesAn ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with agricultural activity finds an elevated risk for malignant bone tumors (OR 2.3) and for subtype osteosarcoma (OR 2.7) at high agricultural activity (greater than 60% of county acreage devoted to farming). Also linked to Ewing’s sarcoma (OR 4.3) and HL (OR 2.1) at high agricultural activity (greater than 60% of county acreage devoted to farming), and for oat crop acreage and Ewing’s (OR 2.3).[Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]

Non-Hodgkin lymphoma among Brazilian agricultural workers: A death certificate case-control study.To estimate the non-Hodgkin lymphoma (NHL) mortality risk among agricultural workers in Brazil's southern states, we used death certificates to identify cases of NHL between the ages of 20 and 69 years from residents of nonurban municipalities between 1996 and 2005 (n = 1,317). Controls were randomly selected from those whose underlying cause of death did not include neoplasm or hematological diseases and paired with cases by sex, age, year of death, and state of residence (n = 2,634). Odds of being an agricultural worker among cases and controls were estimated by conditional logistic regression, stratified and adjusted by sex, state, education, and race. An increased risk of death by NHL was observed among agricultural workers 20-39 years old (ORadj = 2.06; 95% CI 95%, 1.20-3.14). Our results suggest that the young agricultural workers from southern Brazil were more likely to die of NHL compared to nonagricultural workers.[Boccolini PM, Boccolini CS, Chrisman JR, et al. 2017. Arch Environ Occup Health. 72(3):139-144]

Analysis of Environmental Chemical Mixtures and Non-Hodgkin Lymphoma Risk in the NCI-SEER NHL Study.There are several suspected environmental risk factors for non-Hodgkin lymphoma (NHL). The associations between NHL and environmental chemical exposures have typically been evaluated for individual chemicals. Study determined the association between a mixture of 27 correlated chemicals measured in house dust and NHL risk.A population-based case-control study of NHL in four National Cancer Institute-Surveillance, Epidemiology, and End Results centers-Detroit, Michigan; Iowa; Los Angeles County, California; and Seattle, Washington-from 1998 to 2000 was conducted. The WQS index was statistically significantly associated with NHL overall and in the study sites of Detroit, Los Angeles, and Iowa. The most highly weighted chemicals for predicting risk overall were PCB congener 180 and propoxur. Highly weighted chemicals varied by study site; PCBs were more highly weighted in Detroit, and pesticides were more highly weighted in Iowa. An index of chemical mixtures was significantly associated with NHL. Results show the importance of evaluating chemical mixtures when studying cancer risk.[Czarnota J, Gennings C, Colt JS, De Roos AJ, et al. 2015. Environ Health Perspect. 123(10):965-70]

Insecticide exposure and farm history in relation to risk of lymphomas and leukemias in the Women's Health Initiative observational study cohort.In questionnaires, women self-reported history living or working on a farm, personally mixing or applying insecticides, insecticide application in the home or workplace by a commercial service, and treating pets with insecticides. Relationships with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, plasma cell neoplasms, and myeloid leukemia were investigated. The analysis included 76,493 women and 822 NHL cases. Women who ever lived or worked on a farm had 1.12 times the risk of NHL compared to those who did not. Women who reported that a commercial service ever applied insecticides in their immediate surroundings had 65% higher risk of CLL/SLL. Women aged less than 65 years who ever applied insecticides had 87% higher risk of DLBCL. Insecticide exposures may contribute to risk of CLL/SLL and DLBCL.[Schinasi LH, De Roos AJ, Ray RM, Edlefsen KL, et al. 2015. Ann Epidemiol. 25(11):803-810.e4]

Soft tissue sarcoma, non-Hodgkin's lymphoma and chronic lymphocytic leukaemia in workers exposed to phenoxy herbicides: extended follow-up of a UK cohort.Study aimed to provide further information on the possible carcinogenicity of phenoxy herbicides, and in particular their relationship to soft tissue sarcoma (STS), non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL). Authors extended follow-up to December 2012 for 8036 men employed at five factories in the UK which had manufactured phenoxy herbicides, or in a contract spraying business. Mortality from all causes and all cancers was close to expectation, but an excess of deaths from NHL was observed among men who had worked for ≥1 year in jobs with more than background exposure to phenoxy herbicides (19 deaths, SMR 1.85, 95% CI 1.12 to 2.89). Four deaths from STS occurred among men potentially exposed above background (3.3 expected). Findings are consistent with the current balance of epidemiological evidence. If phenoxy herbicides pose a hazard of either STS or NHL, then any absolute increase in risk is likely to be small.[Coggon D, Ntani G, Harris EC, et al. 2015. Occup Environ Med.72(6):435-41.]

Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis.This paper describes results from a systematic review and a series of meta-analyses of nearly three decades worth of epidemiologic research on the relationship between non-Hodgkin lymphoma (NHL) and occupational exposure to agricultural pesticide active ingredients and chemical groups. Estimates of associations of NHL with 21 pesticide chemical groups and 80 active ingredients were extracted from 44 papers, all of which reported results from analyses of studies conducted in high-income countries. Random effects meta-analyses showed that phenoxy herbicides, carbamate insecticides, organophosphorus insecticides and the active ingredient lindane, an organochlorine insecticide, were positively associated with NHL. In a handful of papers, associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate. Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure. Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world's agriculture, were missing in the literature that were reviewed.[Schinasi L, Leon ME. 2014. Int J Environ Res Public Health. 11(4):4449-527.]

Non-hodgkin lymphoma risk and insecticide, fungicide and fumigant use in the agricultural health study.Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). Study evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL and MM) in a U.S.-based prospective cohort of farmers and commercial pesticide applicators. For total NHL, statistically significant positive exposure-response trends were seen with lindane and DDT. Terbufos was associated with total NHL in ever/never comparisons only. In subtype analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukemia/marginal cell lymphoma, lindane and diazinon with follicular lymphoma, and permethrin with MM. However, tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any pesticide. Because 26 pesticides were evaluated for their association with NHL and its subtypes, some chance finding could have occurred. Results showed pesticides from different chemical and functional classes were associated with an excess risk of NHL and NHL subtypes, but not all members of any single class of pesticides were associated with an elevated risk of NHL or NHL subtypes. These findings are among the first to suggest links between DDT, lindane, permethrin, diazinon and terbufos with NHL subtypes.[Alavanja MC, Hofmann JN, Lynch CF, Hines CJ, et al. 2014. PLoS One. 9(10):e109332]

Exposures to multiple pesticides and the risk of Hodgkin lymphoma in Canadian men.Study's aim was to determine the risk of Hodgkin lymphoma (HL) associated with exposures to multiple pesticides grouped by various classes, including carcinogenic classifications. Data collected in the Cross-Canada Study of Pesticides and Health, a population-based incident case-control study in six provinces conducted between 1991 and 1994, were analyzed using unconditional logistic regression. Overall, there was an increase in the risk of HL among all subjects who reported use of five or more insecticides (OR 1.88) and among subjects younger than 40 who reported use of two acetylcholinesterase inhibitors (OR 3.16). There was an elevated odds ratio associated with reported use of three or more probably carcinogenic pesticides (OR 2.47), but no increase in risk for use of possibly carcinogenic pesticides. The risk of HL from reported use of fungicides or any pesticides was greater for cases diagnosed before age 40 than for cases diagnosed at or after age 40. This study found associations between HL and fungicides, insecticides, specifically acetylcholinesterase inhibitors, and pesticides previously identified as probable human carcinogens.[Navaranjan G, Hohenadel K, Blair A, Demers PA, et al. 2013. Cancer Causes Control. 24(9):1661-73]

Hypospadias and residential proximity to pesticide applications.Examine the association of hypospadias with residential proximity to commercial agricultural pesticide applications.The study population included male infants born from 1991 to 2004 to mothers residing in 8 California counties. Cases (n = 690) were ascertained by the California Birth Defects Monitoring Program; controls were selected randomly from the birth population (n = 2195). Authors determined early pregnancy exposure to pesticide applications within a 500-m radius of mother's residential address, using detailed data on applications and land use. Forty-one percent of cases and controls were classified as exposed to 57 chemical groups and 292 chemicals. Despite >500 statistical comparisons, there were few elevated odds ratios with confidence intervals that excluded 1 for chemical groups or specific chemicals. Those that did were for monochlorophenoxy acid or ester herbicides; the insecticides aldicarb, dimethoate, phorate, and petroleum oils; and adjuvant polyoxyethylene sorbitol among all cases; 2,6-dinitroaniline herbicides, the herbicide oxyfluorfen, and the fungicide copper sulfate among mild cases; and chloroacetanilide herbicides, polyalkyloxy compounds used as adjuvants, the insecticides aldicarb and acephate, and the adjuvant nonyl-phenoxy-poly(ethylene oxy)ethanol among moderate and severe cases. Odds ratios ranged from 1.9 to 2.9.Most pesticides were not associated with elevated hypospadias risk. For the few that were associated, results should be interpreted with caution until replicated in other study populations.[Carmichael SL, Yang W, Roberts EM, et al. 2013. Pediatrics. 132(5):e1216-26]

Non-Hodgkin lymphoma and pesticide exposure in Turkey.The study used data from 1995 to 2010 on the patients who were histopathologically diagnosed with NHL during these years. An increase in the NHL incidence over the years was identified, with a 2.42-fold increment found from 1995 to 2005 and a 2.77 fold elevation from 1995 to 2010. The use of pesticides increased 1.89 fold over the same period.Study investigated the relationship of the pesticides used with NHL patients diagnosed during the same year. Since the time elapsing after exposure to pesticides until the development of cancer is not clear, no comparison can be made at present. We believe that the increase in use of pesticides since 1995 may be associated with the increase in the incidence of NHL and therefore that further studies on the issue including measurements of serum pesticide levels, are required.[Yildirim M, Karakilinc H, Yildiz M, Kurtoglu E, et al. 2013. Asian Pac J Cancer Prev. 14(6):3461-3.]

Non-hodgkin's lymphoma and work in agriculture: Results of a two case-control studies in Saskatchewan, Canada.The objective was to examine the association between non-Hodgkin's lymphoma (NHL) and farming-related activities, gender, pesticides exposure, and exposure to chemicals other than pesticides in Saskatchewan. Male and female study participants were taken from two separate case-control studies conducted in Saskatchewan province, Canada. A case was defined as any man or woman aged 19 years and older with a first diagnosis of NHL registered by the Saskatchewan Cancer Agency during the study period. Farming exposure and exposure to pesticides-contaminated cloths were related to an increased risk of NHL. Exposure to pesticides was strongly associated with an increased risk of NHL, especially for men.[Karunanayake CP, Dosman JA, Pahwa P. 2013. Indian J Occup Environ Med.17(3):114-21]

Pesticide use and non-Hodgkin's lymphoma mortality in Brazil.Brazil is one of the major pesticide consumers in the world. The continuous exposure to these substances may be etiologically associated with the development of Non-Hodgkin's Lymphoma (NHL). Study's goal was to Estimate the correlation between the per capita sales of pesticides in 1985 (exposure) and NHL mortality rates between 1996 and 2005 (outcome), by Brazilian micro-regions. A moderate correlation between per capita pesticides consumption and standardized mortality rate for NHL was observed (r=0.597). In addition, using the lowest quartile of pesticide consumption as a reference, the higher the quartile of pesticide consumption, the higher was NHL mortality risk: men - (second quartile - MRR=1.69, CI 95% 1.68-1.84; third quartile - MRR=2.41, CI 95% 2.27-2.57; fourth quartile - MRR=2.92, CI 95% 2.74-3.11) and females (second quartile - MRR=1.87, CI 95% 1.69-2.06; third quartile - MRR=2.28, IC 95% 2.10-2.47; fourth quartile - MRR=3.20; CI 95% 2.98-3.43).Results suggest that pesticide exposure may play a role in the etiology of NHL.[Boccolini Pde M, Boccolini CS, Chrisman Jde R, et al. 2013. Int J Hyg Environ Health. 216(4):461-6.]

A prospective study of organochlorines in adipose tissue and risk of non‑Hodgkin lymphoma.Purpose here was to examine associations between organochlorine concentrations in prediagnostic adipose tissue samples and the risk of NHL.Authors conducted a case–cohort study using a prospective Danish cohort of 57,053 persons enrolled between 1993 and 1997 and measured concentrations of 8 pesticides and 10 polychlorinated biphenyl (PCB) congeners in adipose tissue collected upon enrollment. Results found a higher risk of NHL in association with higher adipose tissue levels of DDT, cis-nonachlor, and oxychlordane, but no association with PCBs. This is the first study of organochlorines and NHL using prediagnostic adipose tissue samples in the exposure assessment and provides new environmental health evidence that these organochlorines contribute to NHL risk.[Bräuner EV, Sørensen M, Gaudreau E, LeBlanc A, et al. 2012. Environ Health Perspect.120(1):105-11.]

Pesticide use, immunologic conditions, and risk of non-Hodgkin lymphoma in Canadian men in six provinces.Pesticide exposures and immune suppression have been independently associated with the risk of non-Hodgkin lymphoma (NHL), but their joint effect has not been well explored. Data from a case-control study of men from six Canadian provinces were used to evaluate the potential effect modification of asthma, allergies, or asthma and allergies and hay fever combined on NHL risk. Incident NHL cases (n = 513) diagnosed between 1991 and 1994 were recruited from provincial cancer registries and hospitalization records and compared to 1,506 controls. Subjects with asthma, allergies, or hay fever had non-significantly elevated risks of NHL associated with use of MCPA (OR = 2.67) compared to subjects without any of these conditions (OR = 0.81). Conversely, those with asthma, allergies, or hay fever who reported use of malathion had lower risks of NHL (OR = 1.25) versus subjects with none of these conditions (OR = 2.44). Similar effects were observed for asthma and allergies evaluated individually. Although there were some leads regarding effect modification by these immunologic conditions on the association between pesticide use and NHL, small numbers, measurement error and possible recall bias limit interpretation of these results.[Pahwa M, Harris SA, Hohenadel K, McLaughlin JR, et al.2012.Int J Cancer. 131(11):2650-9.]

Mortality of US pentachlorophenol production workers through 2005.A cohort of 2122 US pentachlorophenol (PCP) production workers from four plants in the National Institute for Occupational Safety and Health Dioxin Registry was exposed to PCP and to polychlorinated dibenzo-p-dioxin and dibenzofuran contaminants of PCP production. A subcohort of 720 was also exposed to 2,3,7,8-tetrachlorodibenzodioxin, a contaminant of trichlorophenol (TCP) while using TCP or a TCP derivative. PCP and several production contaminants have been implicated as animal carcinogens. A priori hypotheses were that the cohort would have elevated standardized mortality ratios (SMRs) for aplastic anemia, soft-tissue sarcoma, and non-Hodgkin lymphoma, as suggested by human studies, and for leukemia and liver, adrenal, thyroid, and parathyroid cancer, as suggested by animal studies. From 1940 to 2005 1165 deaths occurred with an overall SMR of 1.01 [95% confidence limits (CI), 0.95-1.07]. Overall cancer mortality (326 deaths, SMR 1.17, CI 1.05-1.31) was in statistically significant excess. There were excess deaths for trachea, bronchus and lung cancers (126 deaths, SMR 1.36, CI 1.13-1.62), non-Hodgkin lymphoma (17 deaths, SMR 1.77, CI 1.03-2.84), chronic obstructive pulmonary disease (63 deaths, SMR 1.38, CI 1.06-1.77), and medical complications (5 deaths, SMR 3.52, CI 1.14-8.22).The excess of cancers of a priori interest, non-Hodgkin lymphoma and leukemia, provide some support for the carcinogenicity of PCP, however, further studies with more detailed exposure assessment are needed.[Ruder AM, Yiin JH. 2011.Chemosphere. 83(6):851-61.]

Occupational exposure to terbufos and the incidence of cancer in the Agricultural Health StudyStudy investigated associations between use of terbufos and the incidence of cancer. The Agricultural Health Study is a prospective cohort study of 57,310 licensed pesticide applicators from Iowa and North Carolina. Detailed information about 50 pesticides, including terbufos, and potential confounders was obtained from self-administered questionnaires. Overall cancer risk was slightly increased among terbufos users. Suggestive associations were observed between terbufos use and cancers of the prostate and lung, leukemia, and non-Hodgkin's lymphoma, although the exposure-response gradients were non-monotonic and p for trends were not significant. However, cautious interpretation of these results is warranted by the lack of existing experimental and epidemiologic evidence to support carcinogenic effects of terbufos.[Bonner, M.R., et al. 2010. Cancer Causes Control 21(6):871-7]

Pesticide exposure as risk factor for non-Hodgkin lymphoma including histopathological subgroup analysis.A Swedish population based case-control study of male and female NHL patients finds the highest risk is for exposure to: herbicides; MCPA with a latency period greater than ten years; glyphosate ; and, glyphosate exposure with a latency period of greater than ten years . When different NHL subtypes are analyzed: (a) diffuse large B-cell lymphoma is significantly associate with exposure to phenoxyacetic acids and especially for MCPA; (b) small lymphocytic lymphoma/chronic lymphocytic leukemia is associated with exposure to phenoxy herbicides, MCPA , and glyphosate ; (c) the category “other specific B-cell lymphoma (mantle cell lymphoma, marginal zone lymphoma)” an association is found for exposure to phenoxyacetic acids, MCPA and glphyosate; and (d) the category “unspecific NHL” subtypes are associated with herbicides, phenoxyacetic acids, MCPA and glyphosate.[Eriksson, M., et al. 2008. Int J Cancer 123(7):1657-1663]

Atopy, exposure to pesticides and risk of non-Hodgkin lymphomaAlthough the Australian population based case control study did not find a clear connection with asthma and pesticide exposure and NHL, it did find an increased risk of NHL with occupational pesticide exposure and a history of asthma as well as with occupational pesticide exposure an no history of asthma.[Vajdic, C.M., et al. 2007. Int J Cancer 120(10):2271-2274]

Agricultural pesticide use and risk of t(14;18)-defined subtypes of non-Hodgkin lymphoma.A population based, case control study in Nebraska looking at different molecular subtypes of NHL discovered that the risk of t(14;18)-positive NHL subtype is significantly elevated among farmers who used animal insecticides (OR 2.6), crop insecticides (OR 3.0), herbicides (OR 2.9) and fumigants (5.0 OR) and that there was no increased risk of t(14;18)-negative NHL subtype for these pesticides, which may explain some of the inconsistencies in epidemiological study of NHL and pesticide exposure. They also find that the risk increases with longer duration of use[Chiu, B., et al. 2006. Blood 108(4):1363-1369]

Pesticide exposures in children with non-Hodgkin lymphoma.A case-control study in the U.S. finds a significant association between risk of childhood NHL and frequency of reported prenatal home pesticide use, and professional treatments in the home. Postnatal home pesticide exposure also shows a significant association . In children, elevated risk for T-cell, B-cell lymphomas, lymphoblastic, large cell, and Burkitt morphologies are found.[Buckley, J.D., et al. 2000. Cancer 89(11):2315-2321]

Cancer incidence among Icelandic pesticide usersA small cohort study in Iceland shows that female licensed pesticide applicators for agricultural purposes have a significant increased incidence for cancers of the lymphatic and hematopoietic tissue in women.[Zhong, Y. and Rafnsson, V. 1996. International Journal of Epidemiology 25(6):1117-1124.]

Farming, pesticide use and hairy-cell leukemia.A significant association is found between HCL and exposure to pesticides used in farming (OR ranges between 1.5 to 2.4, depending on the type of pesticide). Orgaonphosphates were positively associated with HCL.[Clavel, J., et al. 1996. Scand J Work Environ Health 22(4):285-293]

The role of agricultural pesticide use in the development of non-Hodgkin's lymphoma in womenA population-based case control study in Nebraska finds that NHL risk is significantly increased for woman who handle OP insecticides, for use of chlorinated hydrocarbon insecticides, and for chlorinated hydrocarbon insecticide use on cattle. The study finds that pesticide related risk are grater for woman with a family history of cancer.[Zahm, S., et al. 1993. Archives of Environmental Health 48(5):353-358]

Pesticides and Other Agricultural Risk Factors for Non-Hodgkin's Lymphoma among Men in Iowa and MinnesotaA population based study of white male farmers finds a significant increase in risk for (a) diffuse NHL and organophosphates (OP) on crops, non-halogenated aliphatic OP on crops, cyclodiene chlorinated hydrocarbons used on livestock, and triazine herbicides; (b) small lymphocytic NHL with “natural product insecticides used on livestock” (although nowhere in the study does it define “natural”), and halongenated aromatic OP for livestock); and, (c) other and unclassified forms of NHL and chlorinated hydrobarbon insecticides for crops, cyclodienes for crops, and halogenated aliphatic OPs used on livestock[Cantor, K., et al. 1992. Cancer Research 52:2447-2455]

Cancer mortality in the U.S. flour industryA nested case control mortality study of workers employed in U.S. flour mills, where according to the study author’s, “pesticides are used more frequently than in other segments of the industry,” an increased risk for NHL (OR 4.2) is found.[Alavanja, M.C., et al. 1990. J Natl Cancer Inst 82(10):840-848]

Agricultural herbicide use and a risk of lymphoma and soft-tissue sarcoma.A population based case control study in Kansas finds farm herbicide use increases risk associated with NHL; risk increased significantly for those men exposed to herbicides more than 20 days a year; and, those men that frequently mixed or applied herbicides themselves also have a significant increased risk to phenoxyacetic acid herbicides, specifically 2,4D.[Hoar, S., et al. 1986. Journal of the American Medical Association 259(9): 1141-1147]

A Review of the Association Between Parkinson Disease and Malignant MelanomaAn association between melanoma and Parkinson disease (PD) has been hinted at in the neurology and oncology literature since the 1970s after the initiation of levodopa (L-DOPA) therapy for PD. Given that L-DOPA is a substrate in melanin synthesis, there existed a concern that this therapy might cause melanoma.The objective was to research possible etiological links to explain the connection between PD and melanoma. Patients with PD have an overall decreased risk of cancer diagnoses. However, breast cancer and melanoma have an uncharacteristically high rate of co-occurrence with PD. Family history of melanoma and lighter hair and skin color confer a higher risk of developing PD, and having a first-degree relative with either disease conveys a significantly increased risk of developing the other. Other possible connections that have been explored include pigmentation genes in neural-derived cells, pesticides, MC1R polymorphisms, and abnormal cellular autophagy. Although a link between PD and melanoma exists, the etiology of this link continues to be elusive. Both PD and melanoma are likely multifactorial diseases involving genetic and environmental risk factors.[Disse M, Reich H, Lee PK, Schram SS. 2016. Dermatol Surg. 42(2):141-6.]

Occupational Exposure to Pesticides With Occupational Sun Exposure Increases the Risk for Cutaneous Melanoma.The objective of the study was to examine the association between occupational exposure to pesticides and cutaneous melanoma, controlling for all possible confounders.A pooled analysis of two case-control studies was conducted in two different geographic areas (Italy and Brazil). Detailed pesticides exposure histories were obtained. Ever use of any pesticide was associated with a high risk of cutaneous melanoma (odds ratio 2.58; 95% confidence interval 1.18-5.65) in particular exposure to herbicides (glyphosate) and fungicides (mancozeb, maneb), after controlling for confounding factors. When subjects were exposed to both pesticides and occupational sun exposure, the risk increased even more (odds ratio 4.68; 95% confidence interval 1.29-17.0). The study suggests an augmented risk of cutaneous melanoma among subjects with exposure to pesticides, in particular among those exposed to occupational sun exposure.[Fortes C, Mastroeni S, Segatto M M, Hohmann C, et al. 2016. J Occup Environ Med. 58(4):370-5. ]

Residential and occupational exposure to pesticides may increase risk for cutaneous melanoma: a case-control study conducted in the south of Brazil.Incidences of primary cutaneous melanoma (CM) have risen over the last few decades, mainly among populations of White European extraction. Some risk factors for melanoma have been clearly established, but other potential risk factors, such as exposure to pesticides, are currently under study.A case-control study on melanoma was conducted during 2012 and 2013 at three dermatological reference centers in Porto Alegre, Brazil. A total of 191 CM patients and sex- and age-matched control subjects were enrolled in the study. Subjects exposed to pesticides had twice the level of risk for melanoma (odds ratio [OR] 2.03). When pesticides were used indoors for >10 years, the risk for CM increased further (OR 2.84). A high frequency of indoor use of pesticides (four or more times per year) was associated with a 44% increase in the risk for melanoma (OR 1.44). The domestic use of pesticides outdoors was not associated with increased risk. Subjects exposed to pesticides at an occupational level were at four times greater risk than subjects who were not occupationally exposed (OR 4.23).These findings indicate that the general use of pesticides, particularly indoor domestic use, frequently and over a long period, may be an independent environmental risk factor for CM.[Segatto MM, Bonamigo RR, Hohmann CB, Müller KR, et al. 2015. Int J Dermatol. doi: 10.1111/ijd.12826]

Specific pesticide-dependent increases in α-synuclein levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines.Epidemiological studies indicate a role of genetic and environmental factors in Parkinson's disease involving alterations of the neuronal α-synuclein (α-syn) protein. Objective was to precisely assess changes in α-syn levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines following acute exposure to pesticides (rotenone, paraquat, maneb, and glyphosate). These human cell lines express α-syn endogenously, and overexpression of α-syn (wild type or mutated A53T) can be obtained following recombinant adenoviral transduction. Study found that endogenous α-syn levels in the SH-SY5Y neuroblastoma cell line were markedly increased by paraquat, and to a lesser extent by rotenone and maneb, but not by glyphosate. Rotenone also clearly increased endogenous α-syn levels in the SK-MEL-2 melanoma cell line. In the SH-SY5Y cell line, similar differences were observed in the α-syn adenovirus-transduced cells, with a higher increase of the A53T mutated protein. Paraquat markedly increased α-syn in the SK-MEL-2 adenovirus-transduced cell line, similarly for the wild-type or A53T proteins. Data support the hypothesis that pesticides can trigger some molecular events involve malignant melanoma that consistently shows a significant but still unexplained association with Parkinson's disease.[Chorfa A, Bétemps D, Morignat E, Lazizzera C, et al. 2013. Toxicol Sci. 133(2):289-97.]

Plasma levels of polychlorinated biphenyls and risk of cutaneous malignant melanoma: a preliminary study.This preliminary study examined the relationship between organochlorine compounds(OCC) residues in plasma and risk of cutaneous malignant melanoma (CMM) adjusting for sun sensitivity and sun exposure. A case-control study of 80 CMM patients and 310 control subjects was conducted. Lifetime sun exposure information, along with data on pigmentation variables and sun sensitivity data was collected, along with a blood sample. Strong associations were seen between risk of CMM and plasma levels of non-dioxin-like PCBs (Adjusted OR = 7.02) and several PCB congeners, organochlorine pesticides or metabolites. These associations persisted after control for sun sensitivity and sun exposure. Results from this investigation require independent confirmation in larger studies. However, they suggest that environmental factors other than UV radiation may play a role in genesis of CMM, and indicate that it may be productive to search for further agents which might increase risk.[Gallagher RP, Macarthur AC, Lee TK, Weber JP, et al. 2011. Int J Cancer. 128(8):1872-80]

Risk of childhood cancers associated with residence in agriculturally intense areas in the United StatesAn ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with agricultural activity finds an elevated risk for malignant bone tumors (OR 2.3) and for subtype osteosarcoma (OR 2.7) at high agricultural activity (greater than 60% of county acreage devoted to farming). Also linked to Ewing’s sarcoma (OR 4.3) and HL (OR 2.1) at high agricultural activity (greater than 60% of county acreage devoted to farming), and for oat crop acreage and Ewing’s (OR 2.3).[Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]

Carbaryl exposure and incident cancer in the Agricultural Health StudyUsing the Agricultural Health Study cohort of pesticide applicators and looking at carbaryl exposure, finds that carbaryl exposure is associated with an elevated risk to melanoma, even after adjusting for sunlight exposure.[Mahajan, R., et al. 2007. Int J Cancer 121(8):1799-1805.]

The association between residential pesticide use and cutaneous melanomaA case-control study of cutaneous melanoma finds an increased risk for indoor pesticide use four times a year (OR 2.18) compared to one time a year and for those exposed for 10 years or more an almost two and half times the risk as those exposed for less than 10 years indicating residential pesticide exposure may be a factor for cutaneous melanoma.[Fortes, C., et al. 2007. Eur J Cancer 43(6):1066-1075.]

Pesticide exposures and the risk of multiple myeloma in men: An analysis of the North American Pooled ProjectMultiple myeloma (MM) has been consistently linked with agricultural activities, including farming and pesticide exposures. Three case-control studies in the United States and Canada were pooled to create the North American Pooled Project (NAPP) to investigate associations between pesticide use and haematological cancer risk. This analysis used data from 547 MM cases and 2700 controls. Pesticide use was evaluated as follows: ever/never use; duration of use (years); and cumulative lifetime-days (LD) (days/year handled × years of use). Increased MM risk was observed for ever use of carbaryl (OR = 2.02, 95% CI = 1.28-3.21), captan (OR = 1.98, 95% CI = 1.04-3.77) and DDT (OR = 1.44, 95% CI = 1.05-1.97). Using the Canadian subset of NAPP data, we observed a more than threefold increase in MM risk (OR = 3.18, 95% CI = 1.40-7.23) for ≤10 cumulative LD of carbaryl use. The association was attenuated but remained significant for >10 LD of carbaryl use (OR = 2.44; 95% CI = 1.05-5.64; ptrend = 0.01). For captan, ≤17.5 LD of exposure was also associated with a more than threefold increase in risk (OR = 3.52, 95% CI = 1.32-9.34), but this association was attenuated in the highest exposure category of >17.5 LD (OR = 2.29, 95% CI = 0.81-6.43; ptrend = 0.01). An increasing trend (ptrend = 0.04) was observed for LD of DDT use (LD > 22; OR = 1.92, 95% CI = 0.95-3.88). In this large North American study of MM and pesticide use, we observed significant increases in MM risk for use of carbaryl, captan and DDT.[Presutti R, Harris SA, Kachuri L, Spinelli JJ, et al. 2016. Int J Cancer. 139(8):1703-14.]

Multiple myeloma and glyphosate use: a re-analysis of US Agricultural Health Study (AHS) data.A previous publication of 57,311 pesticide applicators enrolled in the US Agricultural Health Study (AHS) produced disparate findings in relation to multiple myeloma risks in the period 1993-2001 and ever-use of glyphosate (32 cases of multiple myeloma in the full dataset of 54,315 applicators without adjustment for other variables: rate ratio (RR) 1.1, 95% confidence interval (CI) 0.5 to 2.4; 22 cases of multiple myeloma in restricted dataset of 40,719 applicators with adjustment for other variables: RR 2.6, 95% CI 0.7 to 9.4). It seemed important to determine which result should be preferred. RRs for exposed and non-exposed subjects were calculated using Poisson regression; subjects with missing data were not excluded from the main analyses. Using the full dataset adjusted for age and gender the analysis produced a RR of 1.12 (95% CI 0.50 to 2.49) for ever-use of glyphosate. Additional adjustment for lifestyle factors and use of ten other pesticides had little effect (RR 1.24, 95% CI 0.52 to 2.94). There were no statistically significant trends for multiple myeloma risks in relation to reported cumulative days (or intensity weighted days) of glyphosate use. The doubling of risk reported previously arose from the use of an unrepresentative restricted dataset and analyses of the full dataset provides no convincing evidence in the AHS for a link between multiple myeloma risk and glyphosate use.[Sorahan T .2015. Int J Environ Res Public Health. 12(2):1548-59.]

Risk Factors for Multiple Myeloma: A Systematic Review of Meta-AnalysesThis systematic review aims to synthesize meta-analyses examining risk factors for MM so as to provide a comprehensive, parsimonious summary of the current evidence. Eligible meta-analyses were sought in PubMed adopting a predefined. Among the 22 ultimately included meta-analyses, 9 examined occupational factors, 4 assessed aspects of lifestyle (smoking, alcohol, body mass index), 5 evaluated the presence of other diseases, and 4 addressed genetic factors as potential risk factors of MM. A vast compendium of significant associations arose, including farming, exposures to chemicals or pesticides, overweight and obesity, pernicious anemia, gene promoter methylation, and polymorphisms. In conclusion, MM is a multifactorial disease, encompassing a wide variety of risk factors that span numerous life aspects. Further accumulation of evidence through meta-analyses is anticipated in this rapidly growing field.[Sergentanis TN, Zagouri F, Tsilimidos G, et al. 2015. Clin Lymphoma Myeloma Leuk. 15(10):563-577.e3]

Multiple myeloma and occupation: a pooled analysis by the International Multiple Myeloma Consortium.Authors investigated occupational risk of multiple myeloma (MM) in a pooled analysis of five international case-control studies. Gardeners and nursery workers combined, most likely exposed to pesticides, showed a 50% increase in risk (OR = 1.50), while other farming jobs did not. Metal processors, female cleaners, and high level exposure to organic solvents also showed moderately increased risks. Additional case-control studies of MM aetiology are warranted to further investigate the nature of the repeatedly reported increase in MM risk in several occupational groups.[Perrotta C, Kleefeld S, Staines A, Tewari P, De Roos AJ, et al 2013. Cancer Epidemiol.37(3):300-5.]

Multiple pesticide exposures and the risk of multiple myeloma in Canadian menMultiple myeloma (MM) has been linked to certain agricultural exposures, including pesticides. This analysis aimed to investigate the association between lifetime use of multiple pesticides and MM risk using two exposure metrics: number of pesticides used and days per year of pesticide use. A frequency-matched, population-based case-control study was conducted among men in six Canadian provinces between 1991 and 1994. Positive trends in risk were observed for fungicides (ptrend=0.04) and pesticides classified as probably carcinogenic or higher (ptrend=0.03). Excess risks of MM were observed among men who reported using at least one carbamate pesticide (OR=1.94), one phenoxy herbicide (OR=1.56) and ≥3 organochlorines (OR=2.21, 1.05-4.66). Significantly higher odds of MM were seen for exposure to carbaryl (OR=2.71) and captan (OR=2.96). Use of mecoprop for >2 days per year was also significantly associated with MM (OR=2.15). Focusing on multiple pesticide exposures is important because this more accurately reflects how exposures occur in occupational settings. Significant associations observed for certain chemical classes and individual pesticides suggest that these may be MM risk factors.[Kachuri L, Demers PA, Blair A, Spinelli JJ, et al. 2013. Int J Cancer. 133(8):1846-58.]

Multiple myeloma and exposure to pesticides: a Canadian case-control study.The objective of this study was to investigate the putative associations of specific pesticides with multiple myeloma. A matched, population-based, case-control study was conducted among men residing in six Canadian provinces (Quebec, Ontario, Manitoba, Saskatchewan, Alberta, and British Columbia). Exposure to pesticides grouped into major chemical classes resulted in increased risk being detected only for carbamate insecticides. An exposure to fungicide captan was positively associated with the incidence of multiple myeloma. While an exposure to carbaryl was associated with the incidence of multiple myelome with borderline significance. The authors further suggest that certain pesticide exposures may have a role in multiple myeloma etiology, and identify specific factors warranting investigation in other populations.[Pahwa P, Karunanayake CP, Dosman JA, et al. 2012. J Agromedicine. 17(1):40-50.]

Multiple Myeloma and lifetime occupation: results from the EPILYMPH study.The EPILYMPH study applied a detailed occupational exposure assessment approach to a large multi-centre case-control study conducted in six European countries. This paper analysed multiple myeloma (MM) risk associated with level of education, and lifetime occupational history and occupational exposures, based on the EPILYMPH data set.A low level of education was associated with MM. An increased risk was observed for general farmers and cleaning workers adjusting for level of education. Risk was also elevated, although not significant, for printers. Pesticide exposure over a period of ten years or more increased MM risk. These results confirm an association of MM with farm work, and indicate its association with printing and cleaning. While prolonged exposure to pesticides seems to be a risk factor for MM, an excess risk associated with exposure to organic solvents could not be confirmed.[Perrotta C, Staines A, Codd M, Kleefeld S, Crowley D, et al. 2012. J Occup Med Toxicol. 7(1):25.]

Selected cancer mortality and farm practices in IowaA mortality study of Iowan farmers who died between 1964 and 1978 finds an elevated mortality from multiple myeloma in association with herbicide and insecticide use.[Burmeister, L.F., et al. 1983.Am J Epidemiol 118(1):72-77.]

Neuroblastoma

Cytotoxicity induced by cypermethrin in Human Neuroblastoma Cell Line SH-SY5Y.The purpose of this study was to evaluate the cytotoxic potential of Cypermethrin (CM) on cultured human Neuroblastoma SH-SY5Y cells. SH-SY5Y cells were treated with CM at 0-200µM for 24, 48, and 72 h, in vitro. It was found that CM induced the cell death of Neuroblastoma cells in a dose- and time-dependent manner, as shown by LDH assays. Next, some aspects of the process of cell death triggered by CM in the human SH-SY5Y cell line were investigated. It was revealed that the pan-caspase inhibitor Q-VD-OPh, sensitizes SH-SY5Y cells to necroptosis caused by CM. Furthermore, signal transduction inhibitors PD98059, SL-327, SB202190, SP600125 failed to attenuate the effect of the pesticide. Finally, it was shown that inhibition of TNF-a by Pomalidomide (PLD) caused statistically significant reduction in CM-induced cytotoxicity. Overall, the data obtained suggest that CM induces neurotoxicity in SH-SY5Y cells by necroptosis.[Raszewski G, Lemieszek MK, Łukawski K. 2016. Ann Agric Environ Med. 23(1):106-10.]

Risk of childhood cancers associated with residence in agriculturally intense areas in the United StatesAn ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with agricultural activity finds an elevated risk (OR 1.9) for primitive neuroectodermal tumors (central nervous system) at high agricultural activity (greater than 60% of county acreage devoted to farming). Also sympathetic nervous system tumors at high agricultural activity, with subtypes neuroblastomas (OR 1.8) and retinoblastomas (OR 2.6) showing an increased risk.[Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]

Residential pesticide exposure and neuroblastomaHome (OR 1.6) and garden (OR 1.7) pesticide use are associated with neuroblastoma, with a more than double the risk for infants when exposed to garden pesticides.[Daniels, J.L., et al. 2001. Epidemiology 12(1):20-27.]

Oesophageal Cancer

Esophageal cancer among Brazilian agricultural workers: case-control study based on death certificates.In the present study, the magnitude of the association between agricultural working and esophageal cancer mortality was evaluated in a high pesticide use area in Brazil, through a death certificate-based case-control study. Results showed that, in general, agricultural workers were at significantly higher risk to die by esophageal cancer, when compared to non-agricultural workers. Stratified analysis also revealed that the magnitude of such risk was slightly higher among illiterate agricultural workers, and simultaneous adjustment for several covariates showed that the risk was quantitatively higher among younger southern agricultural workers. These results suggest the esophageal cancer may be included among those types of cancer etiologically associated to agricultural working.[Meyer A, Alexandre PC, Chrisman Jde R, et al. 2011. Int J Hyg Environ Health. 214(2):151-5.]

Pesticide sales and adult male cancer mortality in Brazil.A study of pesticides sales in different parts of Brazil and cancer mortality rates a decade later finds a statistically significant correlation between pesticide sales with the mortality rates for leukemia and cancer of the lip, esophagus, pancreas, and prostate.[Chrisman, J.D., et al. 2009. Int J Hyg Environ Health ;212(3):310-21]

Ovarian Cancer

Effects of Endocrine-Disrupting Chemicals and Epigenetic Modifications in Ovarian Cancer: A Review.Ovarian cancer (OC) is a relatively fatal female reproductive malignancy. Since the underlying causes are uncertain, it brings us to believe that both genetic and external factors contribute toward development of this lethal disorder. Exposure to endocrine-disrupting chemicals (EDCs) in the form of occupational usage of pesticides, fungicides, herbicides, plasticizers, cosmetics, and so on is potentially carcinogenic and their ability to cause epigenetic modifications has led us to hypothesize that they may play a catalytic role in OC progression. In response to synthetic chemicals, animal models have demonstrated disturbances in the development of ovaries and steroid hormonal levels but in humans, more research is required. The present review is an attempt to address the impact of EDCs on the hormonal system and gene methylation levels that may lead to malfunctioning of the ovaries which may consequently develop in the form of cancer. It can be concluded that endocrine disruptors do have a potential carcinogenicity and their high proportions in human body may cause epigenetic modifications, prompting ovarian surface epithelium to grow in an abnormal manner.[Samtani R, Sharma N, Garg D. 2017. Reprod Sci. 1933719117711261.]

Atrazine in public water supplies and risk of ovarian cancer among postmenopausal women in the Iowa Women's Health Study.Few studies have evaluated environmental chemical exposures in relation to ovarian cancer. We previously found an increased risk of ovarian cancer among postmenopausal women in Iowa associated with higher nitrate levels in public water supplies (PWS). However, elevated nitrate levels may reflect the presence of other agricultural chemicals, such as atrazine, one of the most commonly detected pesticides in Iowa PWS. We evaluated the association between atrazine in drinking water and incident ovarian cancer (N=145, 1986-2010) among 13 041 postmenopausal women in the Iowa Women's Health Study who used their PWS for ≥11 years as reported in 1989. Average levels of atrazine (1986-1987), nitrate-nitrogen (NO3-N, 1955-1988) and estimated levels of total trihalomethanes (TTHM, 1955-1988) from PWS monitoring data were linked to the participants' cities of residence. Atrazine was detected in water samples from 69 cities where 4155 women (32%) lived and levels were moderately correlated with NO3-N (ρ=0.35) and TTHM (ρ=0.24). Atrazine levels were not associated with ovarian cancer risk with or without adjusting for NO3-N and TTHM levels (p-trend=0.50 and 0.81, respectively). Further, there was no evidence for effect modification of the atrazine association by NO3-N or TTHM levels.In our study with low atrazine detection rates, we found no association between atrazine in PWS and postmenopausal ovarian cancer risk.[Inoue-Choi M, Weyer PJ, Jones RR, Booth BJ, et al. 2016. Occup Environ Med. 73(9):582-7]

Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health StudyOrganophosphates (OPs) are among the most commonly used insecticides. OPs have been linked to cancer risk in some epidemiological studies, which have been largely conducted in predominantly male populations. This study evaluated personal use of specific OPs and cancer incidence among female spouses of pesticide applicators in the prospective Agricultural Health Study cohort. Among 30 003 women, 25.9% reported OP use, and 718 OP-exposed women were diagnosed with cancer during the follow-up period. Any OP use was associated with an elevated risk of breast cancer (RR=1.20, 95% CI 1.01 to 1.43). Malathion, the most commonly reported OP, was associated with increased risk of thyroid cancer (RR=2.04, 95% CI 1.14 to 3.63) and decreased risk of non-Hodgkin lymphoma (RR=0.64, 95% CI 0.41 to 0.99). Diazinon use was associated with ovarian cancer (RR=1.87, 95% CI 1.02 to 3.43).Authors observed increased risk with OP use for several hormonally-related cancers, including breast, thyroid and ovary, suggesting potential for hormonally-mediated effects. This study represents the first comprehensive analysis of OP use and cancer risk among women, and thus demonstrates a need for further evaluation.[Lerro CC, Koutros S, Andreotti G, Friesen MC, et al. 2015. Occup Environ Med. 72(10):736-44]

Exposure to environmental chemicals and heavy metals, and risk of pancreatic cancer.Study examined pancreatic cancer (PC) risk with self-reported exposures to chemicals and heavy metals.The design was a clinic-based, case-control study of data collected from 2000 to 2014 at Mayo Clinic in Rochester, Minnesota, USA. Self-reported regular exposure to pesticides was associated with increased odds of PC (OR 1.21). Regular exposure to asbestos (OR 1.54), benzene (OR 1.70, and chlorinated hydrocarbons (OR 1.63) also was associated with higher odds of PC. These findings add to the limited data suggesting that exposure to pesticides, asbestos, benzene, and chlorinated hydrocarbons may increase PC risk. They further support the importance of implementing strategies that reduce exposure to these substances.[Antwi SO, Eckert EC, Sabaque CV, Leof ER, et al. 2015. Cancer Causes Control. 26(11):1583-91.]

Agricultural pesticide use and pancreatic cancer risk in the Agricultural Health Study Cohort.Pancreatic cancer is a rapidly fatal disease that has been linked with pesticide use. To further examine the potential associations between the use of a number of pesticides and pancreatic cancer, authors conducted a case-control analysis in the Agricultural Health Study, one of the largest prospective cohorts with over 89,000 participants including pesticide applicators and their spouses in Iowa and North Carolina. Among pesticide applicators, 2 herbicides (EPTC and pendimethalin) of the 13 pesticides examined for intensity-weighted lifetime use showed a statistically significant exposure-response association with pancreatic cancer. Applicators in the top half of lifetime pendimethalin use had a 3.0-fold risk compared with never users, and those in the top half of lifetime EPTC use had a 2.56-fold risk compared with never users. Organochlorines were not associated with an excess risk of pancreatic cancer in this study. These findings suggest that herbicides, particularly pendimethalin and EPTC, may be associated with pancreatic cancer.[Andreotti G, Freeman LE, Hou L, Coble J, Rusiecki J, et al. 2009. Int J Cancer. 124(10):2495-500.]

Pesticide sales and adult male cancer mortality in Brazil.A study of pesticides sales in different parts of Brazil and cancer mortality rates a decade later finds a statistically significant correlation between pesticide sales with the mortality rates for leukemia and cancer of the lip, esophagus, pancreas, and prostate.[Chrisman, J.D., et al. 2009. Int J Hyg Environ Health ;212(3):310-21]

Computational study involving identification of endocrine disrupting potential of herbicides: Its implication in TDS and cancer progression in CRPC patients.Several environmental pollutants, including herbicides, act as endocrine disrupting chemicals (EDCs). They can cause cancer, diabetes, obesity, metabolic diseases and developmental problems. Present study was conducted to screen 608 herbicides for evaluating their endocrine disrupting potential. The screening was carried out with the help of endocrine disruptome docking program, http://endocrinedisruptome.ki.si (Kolsek et al., 2013). This program screens the binding affinity of test ligands to 12 major nuclear receptors. As high as 252 compounds were capable of binding to at least three receptors wherein 10 of them showed affinity with at-least six receptors based on this approach. The latter were ranked as potent EDCs. Majority of the screened herbicides were acting as antagonists of human androgen receptor (hAR). A homology modeling approach was used to construct the three dimensional structure of hAR to understand their binding mechanism. Docking results reveal that the most potent antiandrogenic herbicides would bind to hydrophobic cavity of modeled hAR and may lead to testicular dysgenesis syndrome (TDS) on fetal exposure. However, on binding to T877 mutant AR they seem to act as agonists in castration-resistant prostate cancer (CRPC) patients.[Ahmad MI, Usman A, Ahmad M. 2017. Chemosphere. 173:395-403.]

Disruption of aromatase homeostasis as the cause of a multiplicity of ailments: A comprehensive review.Human health is beset with a legion of ailments, which is exacerbated by lifestyle errors. Out of the numerous enzymes in human body, aromatase, a cytochrome P450 enzyme is particularly very critical. Occurring at the crossroads of multiple signalling pathways, its homeostasis is vital for optimal health. Unfortunately, medications, hormone therapy, chemical additives in food, and endocrine-disrupting personal care products are oscillating the aromatase concentration beyond the permissible level. As this enzyme converts androgens (C19) into estrogens (C18), its agitation has different outcomes in different genders and age groups. Some common pathologies associated with aromatase disruption include breast cancer, prostate cancer, polycystic ovary syndrome (PCOS), endometriosis, osteoporosis, ovarian cancer, gastric cancer, pituitary cancer, Alzheimer's disease, schizophrenia, male hypogonadism, and transgender issues. Several drugs, cosmetics and pesticides act as the activators and suppressors of this enzyme. This carefully-compiled critical review is expected to increase public awareness regarding the threats resultant of the perturbations of this enzyme and to motivate researchers for further investigation of this field.[Patel S. 2017. J Steroid Biochem Mol Biol.168:19-25]

High pesticide exposure events and DNA methylation among pesticide applicators in the agricultural health study.Pesticide exposure has been associated with acute and chronic adverse health effects. DNA methylation (DNAm) may mediate these effects. Study evaluated the association between experiencing unusually high pesticide exposure events (HPEEs) and DNAm among pesticide applicators in the Agricultural Health Study (AHS), a prospective study of applicators from Iowa and North Carolina. DNA was extracted from whole blood from male AHS pesticide applicators (n = 695). Questionnaire data were used to ascertain the occurrence of HPEEs over the participant's lifetime. Pyrosequencing was used to quantify DNAm in CDH1, GSTp1, and MGMT promoters, and in the repetitive element, LINE-1. Linear and robust regression analyses evaluated adjusted associations between HPEE and DNAm. Ever having an HPEE (n = 142; 24%) was associated with elevated DNAm in the GSTp1 promoter at CpG7 (chr11:67,351,134; P < 0.01) and for the mean across the CpGs measured in the GSTp1 promoter (P < 0.01). In stratified analyses, elevated GSTP1 promoter DNAm associated with HPEE was more pronounced among applicators >59 years and those with plasma folate levels ≤16.56 ng/mL (p-interaction <0.01); HPEE was associated with reduced MGMT promoter DNAm at CpG2 (chr10:131,265,803; P = 0.03), CpG3 (chr10:131,265,810; P = 0.05), and the mean across CpGs measured in the MGMT promoter (P = 0.03) among applicators >59 years and reduced LINE-1 DNAm (P = 0.05) among applicators with ≤16.56 ng/mL plasma folate. Non-specific HPEEs may contribute to increased DNAm in GSTp1, and in some groups, reduced DNAm in MGMT and LINE-1. The impacts of these alterations on disease development are unclear, but elevated GSTp1 promoter DNAm and subsequent gene inactivation has been consistently associated with prostate cancer.[Rusiecki JA, Beane Freeman LE, Bonner MR, Alexander M, et al. 2017. Environ Mol Mutagen. 58(1):19-29]

Recent advances on bisphenol-A and endocrine disruptor effects on human prostate cancerEndocrine disrupting chemicals (EDCs) are man-made substances widespread in the environment that include, among many others, bisphenol A (BPA), organochlorinated pesticides and hormone derivatives detectable in meat from animals raised in concentrated animal feeding operations. Increasing evidence indicates that EDCs have a negative impact on human health as well as on male and female fertility. They may also be associated with some endocrine diseases and increased incidence of breast and prostate cancer. This review aims to summarize available data on the (potential) impact of some common EDCs, focusing particularly on BPA, prostate cancer and their mechanisms of action. These compounds interfere with normal hormone signal pathway transduction, resulting in prolonged exposure of receptors to stimuli or interference with cellular hormone signaling in target cells. Understanding the effects of BPA and other EDCs as well as their molecular mechanism(s) may be useful in sensitizing the scientific community and the manufacturing industry to the importance of finding alternatives to their indiscriminate use.[Di Donato M, Cernera G, Giovannelli P, et al. 2017. Mol Cell Endocrinol. pii: S0303-7207(17)30158-2. ]

Recent advances on bisphenol-A and endocrine disruptor effects on human prostate cancer.Endocrine disrupting chemicals (EDCs) are man-made substances widespread in the environment that include, among many others, bisphenol A (BPA), organochlorinated pesticides and hormone derivatives detectable in meat from animals raised in concentrated animal feeding operations. Increasing evidence indicates that EDCs have a negative impact on human health as well as on male and female fertility. They may also be associated with some endocrine diseases and increased incidence of breast and prostate cancer. This review aims to summarize available data on the (potential) impact of some common EDCs, focusing particularly on BPA, prostate cancer and their mechanisms of action. These compounds interfere with normal hormone signal pathway transduction, resulting in prolonged exposure of receptors to stimuli or interference with cellular hormone signaling in target cells. Understanding the effects of BPA and other EDCs as well as their molecular mechanism(s) may be useful in sensitizing the scientific community and the manufacturing industry to the importance of finding alternatives to their indiscriminate use.[Di Donato M, Cernera G, Giovannelli P, et al. Mol Cell Endocrinol. pii: S0303-7207(17)30158-2. ]

Atrazine promotes RM1 prostate cancer cell proliferation by activating STAT3 signaling.Atrazine, a widely used pesticide, is frequently detected in soil and surface water, which alarms epidemiologists and medical professionals because of its potential deleterious effects on health. Indeed, atrazine is a potent endocrine disruptor that increases aromatase expression in some human cancer cell lines. Both animal and human studies have suggested that atrazine is possibly carcinogenic, although discrepant results have been reported. In this study, RM1 cells were used to explore the atrazine effects on prostate cancer. Proliferation, migration and invasion of RM1 cells were assessed by colony formation, wound-healing and invasion assays, respectively, after in vitro exposure to atrazine. In addition, an RM1 cell xenograft model was generated to evaluate the effects of atrazine in vivo. To explore the molecular mechanisms, qRT‑PCR, immunohistochemistry, and western blot analyses were employed to detect mRNA and protein levels of STAT3 signaling and cell cycle related proteins, including p53, p21, cyclin B1 and cyclin D1. Interestingly, RM1 cell proliferation was increased after treatment with atrazine, concomitantly with STAT3 signaling activation. These results suggest that atrazine promotes RM1 cell growth in vitro and in vivo by activating STAT3 signaling.[Hu K, Tian Y, Du Y, Huang L, Chen J, et al. 2016. Int J Oncol. 48(5):2166-74]

Epidemiological trends of hormone-related cancers in Slovenia.The incidence of hormone-related cancers tends to be higher in the developed world than in other countries. In Slovenia, six hormone-related cancers (breast, ovarian, endometrial, prostate, testicular, and thyroid) account for a quarter of all cancers. Their incidence goes up each year, breast and prostate cancer in particular. The age at diagnosis is not decreasing for any of the analysed cancer types. The risk of breast cancer is higher in the western part of the country, but no differences in geographical distribution have been observed for other hormone-related cancers. Furthermore, areas polluted with endocrine-disrupting chemicals that affect hormone balance such as PCBs, dioxins, heavy metals, and pesticides, do not seem to involve a greater cancer risk. We know little about how many cancers can be associated with endocrine disruptors, as there are too few reliable exposure studies to support an association.[Zadnik V, Krajc M. Arh Hig Rada Toksikol. 67(2):83-92. ]

Epidemiological trends of hormone-related cancers in Slovenia.The incidence of hormone-related cancers tends to be higher in the developed world than in other countries. In Slovenia, six hormone-related cancers (breast, ovarian, endometrial, prostate, testicular, and thyroid) account for a quarter of all cancers. Their incidence goes up each year, breast and prostate cancer in particular. The age at diagnosis is not decreasing for any of the analysed cancer types. The risk of breast cancer is higher in the western part of the country, but no differences in geographical distribution have been observed for other hormone-related cancers. Furthermore, areas polluted with endocrine-disrupting chemicals that affect hormone balance such as PCBs, dioxins, heavy metals, and pesticides, do not seem to involve a greater cancer risk. We know little about how many cancers can be associated with endocrine disruptors, as there are too few reliable exposure studies to support an association.[Zadnik V, Krajc M. 2016. Arh Hig Rada Toksikol. 67(2):83-92. ]

Exposure to pesticides and prostate cancer: systematic review of the literatureInvestigations about the association between prostate cancer and environmental and/or occupational pesticide exposure have evidenced a possible role of these chemical substances on tumor etiology, related to their action as endocrine disruptors.To assess the association between pesticide exposure and prostate cancer by conducting a systematic review of the scientific literature.The review included 49 studies published between 1993 and 2015. All studies were in English and analyzed exposure to pesticides and/or agricultural activities. Most studies (32 articles) found a positive association between prostate cancer and pesticides or agricultural occupations, with estimates ranging from 1.01 to 14.10.The evidence provided by the reviewed studies indicates a possible association between the development of prostate cancer and pesticide exposure and/or agricultural occupations.[Silva JF, Mattos IE, Luz LL, Carmo CN, Aydos RD. Rev Environ Health. 31(3):311-27. ]

Prostate cancer risk among French farmers in the AGRICAN cohort.Prostate cancer is one of the most frequent cancers among men worldwide. Its etiology is largely unknown, but an increased risk has been repeatedly observed among farmers. Our aim was to identify occupational risk factors for prostate cancer among farmers in the prospective cohort study AGRICAN.Data on lifetime agricultural exposures (type of crops, livestock and tasks including pesticide use, re-entry and harvesting) were collected from the enrolment questionnaire. During the period from enrolment (2005-2007) to 31 December 2009, 1672 incident prostate cancers were identified. We found an increased risk for cattle breeders using insecticides [HR 1.20, 95% confidence interval (95% CI) 1.01-1.42] with a significant dose-response relationship with number of cattle treated (P for trend 0.01). A dose-response relationship was also observed with the number of hogs (P for trend 0.06). We found an excess of prostate cancer risk among people involved in grassland activities, mainly in haymaking (HR 1.18, 95% CI 1.02-1.36). Pesticide use and harvesting among fruit growers were associated with an elevated prostate cancer risk, with a two-fold increased risk for the largest area. For potato and tobacco producers, an elevated prostate cancer risk was observed for almost all tasks, suggesting a link with pesticide exposure since all of them potentially involved pesticide exposure.Our analysis suggests that the risk of prostate cancer is increased in several farming activities (cattle and hog breeding, grassland and fruit-growing) and for some tasks including pesticide use.[Lemarchand C, Tual S, Boulanger M, Levêque-Morlais N, et al. 2016. Scand J Work Environ Health. 42(2):144-52.]

Sex Steroid Hormone Single-Nucleotide Polymorphisms, Pesticide Use, and the Risk of Prostate Cancer: A Nested Case-Control Study within the Agricultural Health Study.Study evaluated whether single-nucleotide polymorphisms (SNPs) involved in hormone homeostasis alter the effect of pesticide exposure on prostate cancer risk. Authors evaluated pesticide-SNP interactions between 39 pesticides and SNPs with respect to prostate cancer among 776 cases and 1,444 controls nested in the Agricultural Health Study cohort. In these interactions included candidate SNPs involved in hormone synthesis, metabolism or regulation (N = 1,100), as well as SNPs associated with circulating sex steroid concentrations, as identified by genome-wide association studies (N = 17). Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. A significant interaction was observed, which was robust to multiple comparison testing, between the herbicide dicamba and rs8192166 in the testosterone metabolizing gene SRD5A1 (p-interaction = 4.0 × 10-5; q-value = 0.03), such that men with two copies of the wild-type genotype CC had a reduced risk of prostate cancer associated with low use of dicamba (OR = 0.62 95% CI: 0.41, 0.93) and high use of dicamba (OR = 0.44, 95% CI: 0.29, 0.68), compared to those who reported no use of dicamba; in contrast, there was no significant association between dicamba and prostate cancer among those carrying one or two copies of the variant T allele at rs8192166. In addition, interactions between two organophosphate insecticides and SNPs related to estradiol metabolism were observed to result in an increased risk of prostate cancer. While replication is needed, these data suggest both agonistic and antagonistic effects on circulating hormones, due to the combination of exposure to pesticides and genetic susceptibility, may impact prostate cancer risk.[Christensen CH1, Barry KH2, Andreotti G3, Alavanja MC, et al. 2016. Front Oncol. 6:237. eCollection 2016.]

Warfarin use and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer.Anticoagulants, especially vitamin K antagonists (VKAs) such as warfarin, have been hypothesized to have antitumor properties, and use of VKAs has been associated with a lower prostate cancer (PCa) risk. This study estimated PCa risk among users of warfarin and other anticoagulants. All anticoagulant use among 78,615 men during 1995-2009 was analyzed. In total, 6537 men were diagnosed with PCa during 1995-2009 (1210 among warfarin users). Compared to non-users, warfarin use was associated with an increased risk of PCa [multivariable-adjusted hazard ratio (HR) = 1.11, 95% confidence interval (CI) 1.01-1.22]. This was limited to short-term, low-dose use, and was not observed in long-term use. A similar overall risk increase was observed for Gleason grade 7-10 PCa. Low-dose, short-term use of warfarin was associated with an increased risk of metastatic PCa. However, the increase in risk vanished with continued use. Compared to other anticoagulants, low-dose use of warfarin was associated with a slightly elevated overall PCa risk (HR = 1.19, 95% CI 1.00-1.43). The increase in risk disappeared in long-term, high-dose use. This study, which included a larger number of PCa cases with warfarin exposure than previous studies, does not support previous notions of decreased risk of PCa among warfarin users. A similar risk of PCa was found among warfarin users and the general population, and no difference in risk was found between warfarin and other anticoagulants.[Kinnunen PT, Murtola TJ, Talala K, Taari K, et al. 2016. Scand J Urol. 50(6):413-419]

Chronic chlorpyrifos exposure does not promote prostate cancer in prostate specific PTEN mutant mice.Environmental factors are likely to interact with genetic determinants to influence prostate cancer progression. The Agricultural Health Study has identified an association between exposure to organophosphorous pesticides including chlorpyrifos, and increased prostate cancer risk in pesticide applicators with a first-degree family history of this disease. Authors used bioluminescence imaging and histopathological analyses to test whether chronic exposure to chlorpyrifos in a grain-based diet for 32 weeks was able to promote prostate cancer development. Chronic exposure to chlorpyrifos in the diet did not promote prostate cancer development in mice despite achieving sufficient levels to inhibit acetylcholinesterase activity in plasma. The mechanistic basis of pesticide-induced prostate cancer may be complex and may involve other genetic variants, multiple genes, or nongenetic factors that might alter prostate cancer risk during pesticide exposure in agricultural workers.[Svensson RU, Bannick NL, Marin MJ, et al. 2013. J Environ Pathol Toxicol Oncol.32(1):29-39]

Farming, reported pesticide use, and prostate cancer.Prostate cancer is the leading cancer type diagnosed in American men and is the second leading cancer diagnosed in men worldwide. Although studies have been conducted to investigate the association between prostate cancer and exposure to pesticides and/or farming, the results have been inconsistent. This study performed a meta-analysis to summarize the association of farming and prostate cancer. Prostate cancer cases were almost four times more likely to be farmers compared with controls with benign prostate hyperplasia. Reported pesticide exposure was inversely associated with prostate cancer, whereas no association with exposure to fertilizers was observed. Our findings confirm that farming is a risk factor for prostate cancer, but this increased risk may not be due to exposure to pesticides.[Ragin C, Davis-Reyes B, Tadesse H, et al. 2013. Am J Mens Health.7(2):102-9]

Genetic susceptibility loci, pesticide exposure and prostate cancer risk.Uncovering SNP (single nucleotide polymorphisms)-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. Authots evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. Among men carrying two T alleles in EH domain binding protein 1 (EHBP1) SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use. Among men carrying two A alleles in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use. In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.[Koutros S, Berndt SI, Hughes Barry K et al. 2013. PLoS One. 8(4):e58195]

Risk of total and aggressive prostate cancer and pesticide use in the Agricultural Health Study.Because pesticides may operate through different mechanisms, the authors studied the risk of prostate cancer associated with specific pesticides in the Agricultural Health Study (1993-2007). With 1,962 incident cases, including 919 aggressive prostate cancers among 54,412 applicators, this is the largest study to date. Three organophosphate insecticides were significantly associated with aggressive prostate cancer: fonofos, malathion and terbufos. The organochlorine insecticide aldrin was also associated with increased risk of aggressive prostate cancer. This analysis has overcome several limitations of previous studies with the inclusion of a large number of cases with relevant exposure and detailed information on use of specific pesticides at 2 points in time. Furthermore, this is the first time specific pesticides are implicated as risk factors for aggressive prostate cancer.[Koutros S, Beane Freeman LE, Lubin JH, et al. 2013. Am J Epidemiol. 177(1):59-74]

Environmental exposures and prostate cancer.Many malignancies have been linked to specific environmental exposures. Several environmental and occupational factors have been studied for an association to prostate cancer (CaP) risk. These include Agent Orange exposure, farming and pesticides, sunlight/ultraviolet radiation, as well as trace minerals used in tire and battery manufacturing. This manuscript reviews the literature on these environmental exposures and CaP.[Mullins JK, Loeb S. 2012. Urol Oncol. 30(2):216-9]

Prostate cancer and toxicity from critical use exemptions of methyl bromide: environmental protection helps protect against human health risks.Authors performed a systematic review of the literature, including in vitro toxicological and epidemiological studies of occupational and community exposure to the halogenated hydrocarbon pesticide methyl bromide. Study focused on toxic (especially chronic) or carcinogenic effects from the use of methyl bromide, on biomonitoring data and reference values. Out of the 542 peer reviewed publications between 1990-2011, 91 referring to toxicity of methyl bromide and 29 using the term "carcinogenic", "neoplastic" or "mutagenic". Overall, exposure to methyl bromide is associated with an increased risk of prostate cancer. Two epidemiological studies have analyzed environmental, non-occupational exposure to methyl bromide providing evidence for its health risk to the general public. Both the epidemiological evidence and toxicological data suggest a possible link between methyl bromide exposure and serious health problems, including prostate cancer risk from occupational and community exposure. The environmental risks of methyl bromide are not in doubt, but also its health risks, especially for genetically predisposed subjects, should not be underestimated.[Budnik LT, Kloth S, Velasco-Garrido M, Baur X. 2012. Environ Health.11:5]

Genetic variation in base excision repair pathway genes, pesticide exposure, and prostate cancer risk.Authors evaluated interactions between 39 pesticides and 394 tag single-nucleotide polymorphisms (SNPs) for 31 BER genes among 776 prostate cancer cases and 1,444 male controls in a nested case-control study of white Agricultural Health Study (AHS) pesticide applicators. The interaction between fonofos and rs1983132 in NEIL3 [nei endonuclease VIII-like 3 (Escherichia coli)], which encodes a glycosylase that can initiate BER, was the most significant overall. Fonofos exposure was associated with a monotonic increase in prostate cancer risk among men with CT/TT genotypes for low and high use compared with no use, whereas fonofos was not associated with prostate cancer risk among men with the CC genotype. These findings regarding fonofos is consistent with previous AHS findings of increased prostate cancer risk with fonofos exposure among those with a family history of prostate cancer. Although requiring replication, our findings suggest a role of BER genetic variation in pesticide-associated prostate cancer risk.[Barry KH, Koutros S, Berndt SI, Andreotti G, et al. 2011. Environ Health Perspect. 119(12):1726-32]

Prostate cancer and ambient pesticide exposure in agriculturally intensive areas in California.In a population-based case-control study in California's intensely agricultural Central Valley (2005-2006), the authors investigated relations between environmental pesticide/fungicide exposure and prostate cancer. In comparison with unexposed persons, increased risks of prostate cancer were observed among persons exposed to compounds which may have prostate-specific biologic effects (methyl bromide and a group of organochlorines) but not among those exposed to other compounds that were included as controls (simazine, maneb, and paraquat dichloride).This study provides evidence of an association between prostate cancer and ambient pesticide exposures in and around homes in intensely agricultural areas. The associations appear specific to compounds with a plausible biologic role in prostate carcinogenesis.[Cockburn M, Mills P, Zhang X, et al. 2011. Am J Epidemiol. 173(11):1280-8]

Prostate cancer risk and exposure to pesticides in British Columbia farmers.Several epidemiologic studies have reported an increased risk of prostate cancer among farmers. The aim of this study was to assess the risk of developing prostate cancer in relation to exposure to specific active compounds in pesticides. A case-control approach was used with 1,516 prostate cancer patients and 4,994 age-matched internal controls consisting of all other cancer sites excluding lung cancer and cancers of unknown primary site. Lifetime occupational history was obtained through a self-administered questionnaire and used in conjunction with a job exposure matrix to estimate the participants' lifetime cumulative exposure to approximately 180 active compounds in pesticides. The significant association between prostate cancer risk and exposure to DDT, simazine, and lindane is in keeping with those previously reported in the literature. Authors also observed a significant excess risk for several active ingredients that have not been previously reported in the literature such as dichlone, dinoseb amine, malathion, endosulfan, 2,4-D, 2,4-DB, and carbaryl. Some findings in this study were not consistent with those reported in the literature, including captan, dicamba, and diazinon. It is possible that these findings showed a real association and the inconsistencies reflected differences of characteristics between study populations.[Band PR, Abanto Z, Bert J, et al.2011. Prostate. 71(2):168-83]

An update of cancer incidence in the Agricultural Health Study.The objective was to reevaluate cancer incidence among Agricultural Health Study participants. A significant excess of prostate cancer was seen for private and commercial applicators. Excesses were observed for lip cancer and multiple myeloma among private applicators from North Carolina and for marginal zone lymphoma among Iowa spouses. Although lower rates of smoking and increased physical activity probably contribute to the lower overall cancer incidence, agricultural exposures including pesticides, viruses, bacteria, sunlight, and other chemicals may increase risks for specific cancer sites.[Koutros S, Alavanja MC, Lubin JH, et al. 2010. J Occup Environ Med. 52(11):1098-105]

Chlordecone exposure and risk of prostate cancer.Study analyzed the relationship between exposure to chlordecone and the risk of prostate cancer. Researchers investigated 623 men with prostate cancer and 671 controls. Exposure was analyzed according to case-control status. Study found a significant increase in the risk of prostate cancer with increasing plasma chlordecone concentration and for cumulative exposure index. Stronger associations were observed among those with a positive family history of prostate cancer and among those who had lived in a Western country. The rs3829125 and rs17134592 allele variants were in complete linkage disequilibrium and were found at low frequency (0.04). Among subjects with plasma chlordecone concentrations above the LD, carriers of the allele variants had a higher risk of prostate cancer.[Multigner L, Ndong JR, Giusti A, et al. 2010. J Clin Oncol. 28(21):3457-62]

Coumaphos exposure and incident cancer among male participants in the Agricultural Health Study (AHS).Previous research in the Agricultural Health Study (AHS) cohort observed a positive association between coumaphos and prostate cancer in men with a family history of prostate cancer. This study was performed to determine the association between coumaphos and other major cancer sites and to explore the consistency of the association with prostate cancer early (1993-1999) and later (2000-2005) in AHS follow-up. This study included 47,822 male licensed pesticide applicators.Approximately 8% of applicators reported use of coumaphos; 8.5% reported a family history of prostate cancer. Cumulative exposure to coumaphos was not associated with cancer risk overall or with any major cancer site including prostate. In men with a family history of prostate cancer, we observed a positive association between ever use of coumaphos and prostate cancer in both early periods of follow-up. Across all years, this association was statistically significant. Coumaphos was not associated with any cancer evaluated here. In men with a family history of disease, there was evidence of an association between coumaphos and prostate cancer, possibly due to genetic susceptibility.[Christensen CH, Platz EA, Andreotti G, et al. 2010. Environ Health Perspect. 118(1):92-6]

Pesticide use modifies the association between genetic variants on chromosome 8q24 and prostate cancer.In the Agricultural Health Study, a prospective study of licensed pesticide applicators,authors observed increased prostate cancer risk with specific pesticide use among those with a family history of prostate cancer. Thus, study evaluated the interaction among pesticide use, 8q24 variants, and prostate cancer risk. The authors estimated odds ratios (OR) and 95% confidence intervals (95% CI) for interactions among 211 8q24 variants, 49 pesticides, and prostate cancer risk in 776 cases and 1,444 controls. Authors observed a significant interaction among variants on chromosome 8q24, pesticide use, and risk of prostate cancer. Insecticides, particularly organophosphates, were the strongest modifiers of risk, although the biological mechanism is unclear. This is the first report of effect modification between 8q24 and an environmental exposure on prostate cancer risk.[Koutros S, Beane Freeman LE, Berndt SI, et al. 2010. Cancer Res. 70(22):9224-33]

Does exposure to agricultural chemicals increase the risk of prostate cancer among farmers?Several studies suggest that farmers may be at increased risk of prostate cancer. The present analysis, based on a large population-based case-control study conducted among men in the Montreal area in the early 1980's, aim at identifying occupational chemicals which may be responsible for such increases. The original study enrolled 449 prostate cancer cases, nearly 4,000 patients with other cancers, as well as 533 population controls. The present analysis was restricted to a study base of men who had worked as farmers earlier in their lives. There were a total of 49 men with prostate cancers, 127 with other cancers and 56 population controls. There was evidence of a two-fold excess risk of prostate cancer among farmers with substantial exposure to pesticides, as compared to unexposed farmers. There was some suggestion, based on few subjects, of increased risks among farmers ever exposed to diesel engine emissions. The results for pesticides are particularly noteworthy in the light of findings from previous studies. Suggestions of trends for elevated risks were noted with other agricultural chemicals, but these are largely novel and need further confirmation in larger samples.[Parent ME, Désy M, Siemiatycki J. 2009. Mcgill J Med. 12(1):70-7]

Pesticide sales and adult male cancer mortality in Brazil.A study of pesticides sales in different parts of Brazil and cancer mortality rates a decade later finds a statistically significant correlation between pesticide sales with the mortality rates for leukemia and cancer of the lip, esophagus, pancreas, and prostate.[Chrisman, J.D., et al. 2009. Int J Hyg Environ Health ;212(3):310-21]

Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancerTwice as many Vietnam veterans exposed to Agent Oragne were identified with prostate cancer (239 vs 124 unexposed men, respectively; (OR 2.19). Individuals who were exposed to Agent Orange had an increased incidence of prostate cancer; developed the disease at a younger age, and had a more aggressive variant than their unexposed counterparts.[Chamie, K., deVere White, R. W., Lee, D., Ok, J. and Ellison, L. M. 2008. Cancer, 113: 2464–2470.]

A case-control study of farming and prostate cancer in African-American and Caucasian menA population-based case-control study in South Carolina finds farming is associated with increase risk of prostate cancer in Caucasians (OR 1.8) but not African-Americans. The study also finds that farmers who mixed or applied pesticides have a greater risk (OR 1.6); and, the increased risk is found only for those farming less than 5 years. The authors conclude that the racial differenc[Meyer, T.E., et al. 2007. Occup Environ Med 64(3):155-160.]

Prostate cancer risk in California farm workersHispanic farmworkers are found to be at an increased risk for prostate cancer when exposed to relatively high levels of certain organochlorines, organophosphates, fumigants and triazine herbicides.[Mills, P.K. and Yang, R. 2003. J Occup Environ Med 45(3):249-258.]

Farming and prostate cancer mortalityA restrospective cohort study of male farmers find an increased risk associationed with acres of farmland sprayed with herbicides and dying from prostate cancer. No other farm activity examined in the study was associated with any detectable pattern of increased or decreased risk.[Morrison, H., et al. 1993. American Journal of Epidemiology 137(3):270-280.]

Soft Tissue Sarcoma

Comparison of questionnaire data and analyzed dioxin concentrations as a measure of exposure in soft-tissue sarcoma studies.Soft-tissue sarcoma is one of the few specific tumors thought to be caused by polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and specifically TCDD. Evidence is, however, based on questionnaire-based case-control studies, and on very few cancer cases in cohort studies at high occupational exposures to chlorophenols or chlorophenoxy acid herbicides with dioxin impurities. Recall bias has been suspected to influence the reporting of exposure, but this possibility has never been adequately put to test. In the present study 87 cancer patients and 308 controls answered a questionnaire asking their exposure to wood preservatives, fungicides and herbicides, and insecticides, and their PCDD/F concentrations were also measured. After matching for age and area 67-69 sarcoma patients and 153-156 controls were available for the study depending on the chemical group, 1-3 controls for each sarcoma patient. Sarcoma patients reported exposure to these chemicals significantly more often than controls did, odds ratios were 6.7 for wood preservatives (p=0.02), 16 for fungicides and herbicides (p=0.01), and 4.9 for insecticides (p=0.06). There was no association, when the analysis was based on measured PCDD/F concentrations (odds ratios close to 1). Although it is not possible to exclude the role of the main chemical as the cause with certainty, the results indicate that recall bias is very likely in previous studies. Thus the causality between contaminant PCDD/Fs and soft tissue sarcoma cannot be considered proven.[Tuomisto J, Airaksinen R, Pekkanen J, et al. 2017. Toxicol Lett. 270:8-11.]

Wartime toxin exposure: recognising the silent killerWartime toxin exposures have been implicated in the genesis of malignancy in war veterans. Agent Orange, one toxin among many, has been linked to malignancy and the subcomponent phenoxyacetic acid has been associated with soft tissue sarcomas (STSs). This case demonstrates the association between a wartime toxin exposure (Agent Orange) and subsequent cancer development. Ultimately, we aim to highlight the importance of simple, specific questions in the patient history to account for previous wartime toxin exposures.[Khan K, Wozniak SE, Coleman J, Didolkar MS. 2016. BMJ Case Rep. pii: bcr2016217438.]

Pesticide sales and adult male cancer mortality in Brazil.A study of pesticides sales in different parts of Brazil and cancer mortality rates a decade later finds a statistically significant correlation between pesticide sales with the mortality rates for leukemia and cancer of the lip, esophagus, pancreas, and prostate.[Chrisman, J.D., et al. 2009. Int J Hyg Environ Health ;212(3):310-21]

Risk of childhood cancers associated with residence in agriculturally intense areas in the United StatesAn ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with agricultural activity finds an elevated risk for soft tissue sarcomas at high agricultural activity (greater than 60% of county acreage devoted to farming). When looking at sub-types, risk increased for rhabdomyosarcomas and category including germ cell, trophoblastic, and gonadal neoplasms. When looking at crop acreage, an increased risk if found for germ cell carcinomas and oat crops.[Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]

Stomach Cancer

Methyl bromide exposure and cancer risk in the Agricultural Health Study.Study used Poisson regression to calculate rate ratios (RR) and 95 % confidence intervals (CI) for associations between methyl bromide use and all cancers combined, as well as 12 specific sites, among 53,588 Agricultural Health Study pesticide applicators with follow-up from 1993 to 2007. A total of 7,814 applicators (14.6 %) used methyl bromide, predominantly before enrollment. Based on 15 exposed cases, stomach cancer risk increased monotonically with increasing methyl bromide use for low and high use compared with no use. No other sites displayed a significant monotonic pattern. Results provide little evidence of methyl bromide associations with cancer risk for most sites examined; however, study observed a significant exposure-dependent increase in stomach cancer risk. Small numbers of exposed cases and declining methyl bromide use might have influenced our findings. Further study is needed in more recently exposed populations to expand on these results.[Barry KH, Koutros S, Lubin JH, et al. 2012. Cancer Causes Control. 23(6):807-18]

Testicular Cancer

Occupational and environmental exposures associated with testicular germ cell tumours: systematic review of prenatal and life-long exposures.Testicular germ cell tumours (TGCT) are the most common cancers in men aged between 15 and 44 years and the incidence has increased steeply over the past 30 years. The rapid increase in the incidence, the spatial variation and the evolution of incidence in migrants suggest that environmental risk factors play a role in TGCT aetiology. The purpose of this review was to summarise the current state of knowledge on occupational and environmental factors thought to be associated with TGCT. After exclusion of duplicate reports, 72 relevant articles were selected; 65 assessed exposure in adulthood, 7 assessed parental exposures and 2 assessed both. Associations with occupation was reported for agricultural workers, construction workers, firemen, policemen, military personnel, as well as workers in paper, plastic or metal industries. Electromagnetic fields, PCBs and pesticides were also suggested. However, results were inconsistent and studies showing positive associations tended to had lower quality ranking using the assessment scale. Current evidence does not allow concluding on existence of any clear association between TGCT and adulthood occupational or environmental exposure. The limitations of the studies may partly explain the inconsistencies observed. The lack of association with adulthood exposure is in line with current hypotheses supporting the prenatal origin of TGCT. Future research should focus on prenatal or early life exposure, as well as combined effect of prenatal and later life exposure. National and international collaborative studies should allow for more adequately powered epidemiological studies. More sophisticated methods for assessing exposure as well as evaluating gene-environment interactions will be necessary to establish clear conclusion.[Béranger R, Le Cornet C, Schüz J, Fervers B. 2013. PLoS One. 8(10):e77130]

Pesticide exposure and serum organochlorine residuals among testicular cancer patients and healthy controls.The incidence of testicular cancer (TC) has been increasing worldwide during the last decades. The reasons of the increase remains unknown, but recent findings suggest that organochlorine pesticides (OPs) could influence the development of TC. A hospital-based case-control study of 50 cases and 48 controls was conducted to determine whether environmental exposure to OPs is associated with the risk of TC, and by measuring serum concentrations of OPs, including p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) isomer and hexachlorobenzene (HCB) in participants. A significant association was observed between TC and household insecticide use. Crude and adjusted ORs for TC were also significantly associated with higher serum concentrations of total OPs in cases compared with controls. These findings give additional support to the results of previous research that suggest that some environmental exposures to OPs may be implicated in the pathogenesis of TC.[Giannandrea F, Gandini L, Paoli D, et al. 2011. J Environ Sci Health B. 46(8):780-7]

Thyroid Cancer

Occupational exposure to pesticides and other biocides and risk of thyroid cancer.The study assessed the associations between occupational exposure to biocides and pesticides and risk of thyroid cancer. Using data from a population-based case-control study involving 462 incident thyroid cancer cases and 498 controls in Connecticut collected in 2010-2011, authors examined the association with occupational exposure to biocides and pesticides through a job-exposure matrix. Individuals who were occupationally ever exposed to biocides had an increased risk of thyroid cancer (OR=1.65, 95% CI 1.16 to 2.35), and the highest risk was observed for the high cumulative probability of exposure (OR=2.18, 95% CI 1.28 to 3.73). The observed associations were similar when restricted to papillary thyroid cancer and well-differentiated thyroid cancer. Stronger associations were observed for thyroid microcarcinomas (tumour size ≤1 cm). No significant association was observed for occupational exposure to pesticides. Study provides the first evidence linking occupational exposure to biocides and risk of thyroid cancer. The results warrant further investigation.[Zeng F, Lerro C, Lavoué J, Huang H, et al. 2017. Occup Environ Med. 74(7):502-510.]

Occupation and thyroid cancer.Here authors review the epidemiology studies of occupations and occupational exposures and thyroid cancer incidence to provide insight into preventable risk factors for thyroid cancer. They summarised the findings of 30 articles that examined thyroid cancer incidence in relation to occupations or occupational exposure. The most studied (19 of 30 studies) and the most consistent associations were observed for radiation-exposed workers and healthcare occupations. Suggestive, but inconsistent, associations were observed in studies of pesticide-exposed workers and agricultural occupations.[Aschebrook-Kilfoy B, Ward MH, Della Valle CT, Friesen MC. 2014. Occup Environ Med. 71(5):366-80]

Nitrate intake and the risk of thyroid cancer and thyroid diseaseStudy finds an increased risk of thyroid cancer with higher average nitrate levels in public water supplies (nitrate is a contaminant of drinking water in agricultural areas) and with longer consumption of water exceeding 5 mg/L nitrate-N (for >or=5 years at >5 mg/L, relative risk = 2.6).[Ward MH, et al. 2010. Epidemiology. 21(3):389-95]

Risk factors of thyroid tumors: role of environmental and occupational exposures to chemical pollutants.The rising incidence of thyroid cancer observed during the last few decades in most western countries is explained in large part by increasing numbers of diagnoses due to changes in medical screening practices. However, beside radiation exposure, exposure to environmental chemicals may also play a role in thyroid cancer etiology and in the increased incidence. This paper presents the main chemicals suspected to induce thyroid tumorigenesis, and epidemiological results on the association between chemical exposure and thyroid tumors.This review found that environmentally abundant chemicals may disrupt thyroid function and/or play a role in tumorigenesis through a variety of mechanisms. Epidemiological results provide insufficient evidence of a causal link between exposure to environmental chemicals and thyroid tumors, but raise the hypothesis of an increased risk of thyroid neoplasm for workers in the leather, wood, and paper industries, and those exposed to certain solvents and pesticides.[Leux C, Guénel P. 2010. Rev Epidemiol Sante Publique.58(5):359-67]

Thyroid disruption: mechanism and clinical implications in human health.Exposure to specific environmental toxins, including polychlorinated biphenyls, dioxins, phthalates, polybrominated diphenyl ethers (PBDEs), and other halogenated organochlorines, has been shown to interfere with the production, transportation, and metabolism of thyroid hormones by a variety of mechanisms. A broad range of chemicals, with structural similarity to thyroid hormone, have been shown to bind to thyroid receptors with both agonist and antagonist effects on thyroid hormone signaling. The incidence of thyroid disease in the United States, particularly for thyroid cancer and thyroid autoimmune disease, is increasing substantially. The evidence for the significant effects of background levels of thyroid-disrupting chemicals, the known pathways for thyroid disruptors, and the evidence and implications for neurodevelopmental damage due to thyroid-disrupting chemicals is reviewed.[Patrick L. 2009. Altern Med Rev. 14(4):326-46]

Mechanism of trifluralin-induced thyroid tumors in rats.Trifluralin has been reported to cause a significant increase in thyroid follicular cell tumors in male Fischer 344 rats. This study was designed to determine the mechanism of thyroid hyperactivity after trifluralin exposure. A group of 15 male Fischer 344 rats were exposed to trifluralin-fortified (6500 ppm) diet for 2 weeks. In the trifluralin treated rats, the serum T3 and T4 levels decreased by 17% and 90%, respectively and TSH increased by 37% more than the control rats. The decrease in total serum T3 and T4 levels in the trifluralin treated rats was due to enhanced peripheral metabolism and an increase in bile flow that results in a compensatory increase in TSH synthesis and secretion. The increased levels of TSH with chronic exposure to trifluralin would exert a continuous stimulation of the thyroid gland leading to cellular hypertrophy and proliferation predisposing to the development of follicular cell tumors in rats.[Saghir SA, Charles GD, Bartels MJ, et al. 2008. Toxicol Lett.180(1):38-45]

Risk of childhood cancers associated with residence in agriculturally intense areas in the United StatesAn ecological study analyzing incidence data from U.S. children ages 0-14 years diagnosed with cancer between 1995 and 2001 and residence in a county with moderate to high agricultural activity finds statistically significantly elevated risk for thyroid carcinomas (OR 3.0) at high agricultural activity (greater than 60 percent of the total county acreage is devoted to farming). An increased risk is also found for thyroid carcinomas and oat crop acreage (OR 2.0).[Carrozza, S.E., et al. 2008. Environ Health Perspect 116(4):559-565.]

A mode of action for induction of thyroid gland tumors by Pyrethrins in the rat.Prolonged treatment with high doses of pyrethrins results in thyroid gland tumors in the rat. To elucidate the mode of action for tumor formation, the effect of pyrethrins on rat thyroid gland, thyroid hormone levels and hepatic thyroxine UDPglucuronosyltransferase activity was investigated. Treatment with pyrethrins and NaPB increased hepatic microsomal thyroxine UDPglucuronosyltransferase activity and serum thyroid stimulating hormone levels (TSH), but reduced serum levels of either thyroxine (T4) and/or triiodothyronine (T3). The effects of pyrethrins in female rats were dose-dependent, with 100 ppm being a no-effect level, and on cessation of treatment were essentially reversible in both sexes. The concordance between the effects of pyrethrins and NaPB suggests that the mode of action for Pyrethrins-induced rat thyroid gland tumors is similar to that of some other non-genotoxic inducers of hepatic xenobiotic metabolism.[Finch JM, Osimitz TG, Gabriel KL, et al. 2006. Toxicol Appl Pharmacol.214(3):253-62]

Uterine Cancer

Levels of persistent organic pollutants in breast milk of Maya women in Yucatan, Mexico.In this study, 24 breast milk samples, obtained from rural Maya women, from municipalities of Yucatan, Mexico, were analyzed for organochlorine pesticide (OCP) residues by gas chromatography. Recent studies have shown that Maya communities have a poor perception about the proper usage and handling of OCP. The karstic soil in this area has a high vulnerability to groundwater pollution by the use of OCP in agriculture and livestock activities. The impact of the ecosystem on human health is much more critical due to the prevailing poverty and a very low educational level of these communities. About 30% of the Maya population consumes water directly from contaminated wells and sinkholes, resulting in a chronic exposure to OCP. The samples served to identify and quantify high levels of OCP residues (18.43 mg/kg of heptachlor epoxide and 1.92 mg/kg of endrin in the metropolitan zone; 2.10 mg/kg of dieldrin, 0.117 mg/kg of endosulfan II, 0.103 mg/kg of heptachlor, 0.178 mg/kg of endrin, and 0.127 mg/kg of endrin aldehyde in the main agricultural zone and on the west coast). The detected levels of OCP residues are a major concern and represent a potential risk to women and children in the region. This could be associated with the high rates of cervical uterine and breast cancer mortality in Yucatan. Thus, regulations on the usage of OCP and their enforcement are necessary, and it is important to establish a yearly monitoring program for OCP residues in breast milk and groundwater, as well as to implement health promotion programs for women in particular and the general population in general.[Polanco Rodríguez ÁG, Inmaculada Riba López M, Angel DelValls Casillas T, et al. 2017. Environ Monit Assess. 189(2):59]

Monitoring of organochlorine pesticides in blood of women with uterine cervix cancerIn Yucatan, Mexico, chronic exposure of Mayan population to pesticides is expected as about 30 per cent are drinking polluted water. Residues of organochlorine pesticides (OCP) were monitored in 18 municipalities of Yucatan with high mortality rates due to uterine cervix cancer. 70 blood samples collected from Mayan women living in livestock, agricultural and metropolitan area were analyzed for OCP. Solid Phase Extraction was performed on C18 cartridges and analyzed by Gas Chromatography with Electron Capture Detector. The results showed that the highest OCP levels were detected in blood of women living in the livestock area. OCP detected were endosulfan I (7.35 μg/mL), aldrin (3.69 μg/mL), 4,4' DDD (2.33 μg/mL), 1.39 and 1.46 μg/mL of δ-HCH. Women from the agricultural area had high concentrations of OCP in their blood, particularly dieldrin (1.19 μg/mL), and 1.26 μg/mL of 4,4' DDE. In the metropolitan area, 0.080 μg/mL of γ-HCH and 0.064 μg/mL of heptachlore were detected. This monitoring study was also based on epidemiological data of uterine cervical cancer. It was found that environmental factors may have facilitated the infiltration of OCP to the aquifer used for potable water supply. These factors in addition to poverty can have impacts on public health. This first exploratory study suggests that monitoring of OCP in human is important for the establishment of health promotion programs. The integrative analysis of both, environmental and social factors would be helpful to characterize the bioaccumulation of pesticides in humans.[Polanco Rodríguez ÁG, Riba López MI, DelValls Casillas TÁ, et al. 2017. Environ Pollut. 220(Pt B):853-862.]

An endocrine-disrupting chemical, fenvalerate, induces cell cycle progression and collagen type I expression in human uterine leiomyoma and myometrial cells.Fenvalerate (Fen), widely used for its high insecticidal potency and low mammalian toxicity, is classified as an endocrine-disrupting chemical. Recently, Fen has received great attention for its adverse effects on human reproductive health. In this study, we found that Fen (10 microM) had a stimulatory effect on the growth of both cell lines at 24 h compared with controls by MTS (p < 0.01) and BrdU (p < 0.01) assays in hormonally responsive uterine leiomyoma (UtLM) cells and normal uterine smooth muscle cells (UtSMC). Data shows that Fen can stimulate the growth of both UtLM cells and UtSMC, which involves a combination of enhanced cell cycle progression and inhibition of apoptosis. Also this compound can increase collagen I expression, at both mRNA and protein levels. Results also indicate that Fen exposure could be considered a novel risk factor for uterine fibroids through molecular mechanisms that do not directly involve the ERs.[Gao X, Yu L, Castro L, Moore AB, et al. 2010. Toxicol Lett. 196(3):133-41]